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Published in: Cancer Microenvironment 3/2011

01-12-2011 | Original Paper

Homing of Cancer Cells to the Bone

Authors: Anjali Mishra, Yusuke Shiozawa, Kenneth J. Pienta, Russell S. Taichman

Published in: Cancer Microenvironment | Issue 3/2011

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Abstract

A variety of tumor cells preferentially home to the bone. The homing of cancer cells to the bone represents a multi-step process that involves malignant progression of the tumor, invasion of the tumor through the extracellular matrix and the blood vessels and settling of the tumor cells in the bone. Gaining a greater understanding as to the mechanisms used by cancer cells in these processes will facilitate the design of drugs which could specifically target the homing process. In this review we will discuss the properties of tumor cells and the bone microenvironment which promote homing of a cancer cell to the bone. We will highlight the different steps and the molecular pathways involved when a cancer cell metastasize to the bone. Since bone is the major home for hematopoietic stem cells (HSCs), we will also highlight the similarities between the homing of cancer and HSC to the bone. Finally we will conclude with therapeutic and early detection strategies which can prevent homing of a cancer cell to the bone.
Literature
1.
go back to reference Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12(20 Pt 2):6243s–6249sPubMed Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12(20 Pt 2):6243s–6249sPubMed
2.
go back to reference Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2(8):584–593PubMed Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2(8):584–593PubMed
3.
go back to reference Jemal A et al (2007) Cancer statistics, 2007. CA Cancer J Clin 57(1):43–66PubMed Jemal A et al (2007) Cancer statistics, 2007. CA Cancer J Clin 57(1):43–66PubMed
4.
go back to reference Mantyh PW et al (2002) Molecular mechanisms of cancer pain. Nat Rev Cancer 2(3):201–209PubMed Mantyh PW et al (2002) Molecular mechanisms of cancer pain. Nat Rev Cancer 2(3):201–209PubMed
5.
go back to reference Coleman RE (1997) Skeletal complications of malignancy. Cancer 80(8 Suppl):1588–1594PubMed Coleman RE (1997) Skeletal complications of malignancy. Cancer 80(8 Suppl):1588–1594PubMed
6.
go back to reference Townson JL, Chambers AF (2006) Dormancy of solitary metastatic cells. Cell Cycle 5(16):1744–1750PubMed Townson JL, Chambers AF (2006) Dormancy of solitary metastatic cells. Cell Cycle 5(16):1744–1750PubMed
7.
go back to reference Morgan TM et al (2009) Disseminated tumor cells in prostate cancer patients after radical prostatectomy and without evidence of disease predicts biochemical recurrence. Clin Cancer Res 15(2):677–683PubMed Morgan TM et al (2009) Disseminated tumor cells in prostate cancer patients after radical prostatectomy and without evidence of disease predicts biochemical recurrence. Clin Cancer Res 15(2):677–683PubMed
8.
go back to reference Braun S et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353(8):793–802PubMed Braun S et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353(8):793–802PubMed
9.
go back to reference Cristofanilli M et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351(8):781–791PubMed Cristofanilli M et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351(8):781–791PubMed
10.
go back to reference Pierga JY et al (2008) Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial. Clin Cancer Res 14(21):7004–7010PubMed Pierga JY et al (2008) Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial. Clin Cancer Res 14(21):7004–7010PubMed
11.
go back to reference Roudier M (2003) Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone. Hum Pathol 34(7):646–653PubMed Roudier M (2003) Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone. Hum Pathol 34(7):646–653PubMed
12.
go back to reference Liu W et al (2009) Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat Med 15(5):559–565PubMed Liu W et al (2009) Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat Med 15(5):559–565PubMed
13.
go back to reference Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med 350(16):1655–1664PubMed Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med 350(16):1655–1664PubMed
14.
go back to reference Guise TA et al (2006) Basic Mechanisms Responsible for Osteolytic and Osteoblastic Bone Metastases. Clin Cancer Res 12(20):6213s–6216sPubMed Guise TA et al (2006) Basic Mechanisms Responsible for Osteolytic and Osteoblastic Bone Metastases. Clin Cancer Res 12(20):6213s–6216sPubMed
15.
go back to reference Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119(6):1420–1428PubMed Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119(6):1420–1428PubMed
16.
go back to reference Vicovac L, Aplin JD (1996) Epithelial-mesenchymal transition during trophoblast differentiation. Acta Anat (Basel) 156(3):202–216 Vicovac L, Aplin JD (1996) Epithelial-mesenchymal transition during trophoblast differentiation. Acta Anat (Basel) 156(3):202–216
17.
go back to reference Zeisberg EM et al (2007) Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med 13(8):952–961PubMed Zeisberg EM et al (2007) Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med 13(8):952–961PubMed
18.
go back to reference Zeisberg M et al (2007) Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem 282(32):23337–23347PubMed Zeisberg M et al (2007) Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem 282(32):23337–23347PubMed
19.
go back to reference Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2(6):442–454PubMed Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2(6):442–454PubMed
20.
go back to reference Mani SA et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715PubMed Mani SA et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715PubMed
21.
go back to reference Morel AP et al (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 3(8):e2888PubMed Morel AP et al (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 3(8):e2888PubMed
22.
go back to reference Lapidot T et al (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648PubMed Lapidot T et al (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648PubMed
23.
go back to reference Al-Hajj M et al (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100(7):3983–3988PubMed Al-Hajj M et al (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100(7):3983–3988PubMed
24.
go back to reference Ginestier C et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555–567PubMed Ginestier C et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555–567PubMed
25.
go back to reference Singh SK et al (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828PubMed Singh SK et al (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828PubMed
26.
go back to reference Ronnov-Jessen L, Petersen OW, Bissell MJ (1996) Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. Physiol Rev 76(1):69–125PubMed Ronnov-Jessen L, Petersen OW, Bissell MJ (1996) Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. Physiol Rev 76(1):69–125PubMed
27.
go back to reference Bierie B, Moses HL (2006) Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 6(7):506–520PubMed Bierie B, Moses HL (2006) Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 6(7):506–520PubMed
28.
go back to reference Kuperwasser C et al (2004) Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA 101(14):4966–4971PubMed Kuperwasser C et al (2004) Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA 101(14):4966–4971PubMed
29.
go back to reference Orimo A et al (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121(3):335–348PubMed Orimo A et al (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121(3):335–348PubMed
30.
go back to reference Stetler-Stevenson WG, Aznavoorian S, Liotta LA (1993) Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol 9:541–573PubMed Stetler-Stevenson WG, Aznavoorian S, Liotta LA (1993) Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol 9:541–573PubMed
31.
go back to reference Sternlicht MD et al (1999) The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98(2):137–146PubMed Sternlicht MD et al (1999) The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98(2):137–146PubMed
32.
go back to reference Karnoub AE et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449(7162):557–563PubMed Karnoub AE et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449(7162):557–563PubMed
33.
go back to reference Goldstein RH et al (2010) Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis. Cancer Res 70(24):10044–10050PubMed Goldstein RH et al (2010) Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis. Cancer Res 70(24):10044–10050PubMed
34.
go back to reference Subarsky P, Hill RP (2003) The hypoxic tumour microenvironment and metastatic progression. Clin Exp Metastasis 20(3):237–250PubMed Subarsky P, Hill RP (2003) The hypoxic tumour microenvironment and metastatic progression. Clin Exp Metastasis 20(3):237–250PubMed
35.
go back to reference John A, Tuszynski G (2001) The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathol Oncol Res 7(1):14–23PubMed John A, Tuszynski G (2001) The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathol Oncol Res 7(1):14–23PubMed
36.
go back to reference Wilson TJ, Singh RK (2008) Proteases as modulators of tumor-stromal interaction: primary tumors to bone metastases. Biochim Biophys Acta 1785(2):85–95PubMed Wilson TJ, Singh RK (2008) Proteases as modulators of tumor-stromal interaction: primary tumors to bone metastases. Biochim Biophys Acta 1785(2):85–95PubMed
37.
go back to reference Bachmeier BE et al (2001) Matrix metalloproteinases (MMPs) in breast cancer cell lines of different tumorigenicity. Anticancer Res 21(6A):3821–3828PubMed Bachmeier BE et al (2001) Matrix metalloproteinases (MMPs) in breast cancer cell lines of different tumorigenicity. Anticancer Res 21(6A):3821–3828PubMed
38.
go back to reference Nakopoulou L et al (2003) MMP-2 protein in invasive breast cancer and the impact of MMP-2/TIMP-2 phenotype on overall survival. Breast Cancer Res Treat 77(2):145–155PubMed Nakopoulou L et al (2003) MMP-2 protein in invasive breast cancer and the impact of MMP-2/TIMP-2 phenotype on overall survival. Breast Cancer Res Treat 77(2):145–155PubMed
39.
go back to reference Eck SM et al (2009) Matrix metalloproteinase-1 promotes breast cancer angiogenesis and osteolysis in a novel in vivo model. Breast Cancer Res Treat 116(1):79–90PubMed Eck SM et al (2009) Matrix metalloproteinase-1 promotes breast cancer angiogenesis and osteolysis in a novel in vivo model. Breast Cancer Res Treat 116(1):79–90PubMed
40.
go back to reference Klein A et al (2009) Identification of brain- and bone-specific breast cancer metastasis genes. Cancer Lett 276(2):212–220PubMed Klein A et al (2009) Identification of brain- and bone-specific breast cancer metastasis genes. Cancer Lett 276(2):212–220PubMed
41.
go back to reference Dong Z et al (2005) Matrix metalloproteinase activity and osteoclasts in experimental prostate cancer bone metastasis tissue. Am J Pathol 166(4):1173–1186PubMed Dong Z et al (2005) Matrix metalloproteinase activity and osteoclasts in experimental prostate cancer bone metastasis tissue. Am J Pathol 166(4):1173–1186PubMed
42.
go back to reference Nabha SM et al (2008) Bone marrow stromal cells enhance prostate cancer cell invasion through type I collagen in an MMP-12 dependent manner. Int J Cancer 122(11):2482–2490PubMed Nabha SM et al (2008) Bone marrow stromal cells enhance prostate cancer cell invasion through type I collagen in an MMP-12 dependent manner. Int J Cancer 122(11):2482–2490PubMed
43.
go back to reference Janowska-Wieczorek A et al (2000) Differential MMP and TIMP production by human marrow and peripheral blood CD34(+) cells in response to chemokines. Exp Hematol 28(11):1274–1285PubMed Janowska-Wieczorek A et al (2000) Differential MMP and TIMP production by human marrow and peripheral blood CD34(+) cells in response to chemokines. Exp Hematol 28(11):1274–1285PubMed
44.
go back to reference Sloane BF (1990) Cathepsin B and cystatins: evidence for a role in cancer progression. Semin Cancer Biol 1(2):137–152PubMed Sloane BF (1990) Cathepsin B and cystatins: evidence for a role in cancer progression. Semin Cancer Biol 1(2):137–152PubMed
45.
go back to reference Sinha AA et al (2001) Ratio of cathepsin B to stefin A identifies heterogeneity within Gleason histologic scores for human prostate cancer. Prostate 48(4):274–284PubMed Sinha AA et al (2001) Ratio of cathepsin B to stefin A identifies heterogeneity within Gleason histologic scores for human prostate cancer. Prostate 48(4):274–284PubMed
46.
go back to reference Brubaker KD et al (2003) Cathepsin K mRNA and protein expression in prostate cancer progression. J Bone Miner Res 18(2):222–230PubMed Brubaker KD et al (2003) Cathepsin K mRNA and protein expression in prostate cancer progression. J Bone Miner Res 18(2):222–230PubMed
47.
go back to reference Testa JE, Quigley JP (1990) The role of urokinase-type plasminogen activator in aggressive tumor cell behavior. Cancer Metastasis Rev 9(4):353–367PubMed Testa JE, Quigley JP (1990) The role of urokinase-type plasminogen activator in aggressive tumor cell behavior. Cancer Metastasis Rev 9(4):353–367PubMed
48.
go back to reference Achbarou A et al (1994) Urokinase overproduction results in increased skeletal metastasis by prostate cancer cells in vivo. Cancer Res 54(9):2372–2377PubMed Achbarou A et al (1994) Urokinase overproduction results in increased skeletal metastasis by prostate cancer cells in vivo. Cancer Res 54(9):2372–2377PubMed
49.
go back to reference Rabbani SA et al (1990) An amino-terminal fragment of urokinase isolated from a prostate cancer cell line (PC-3) is mitogenic for osteoblast-such as cells. Biochem Biophys Res Commun 173(3):1058–1064PubMed Rabbani SA et al (1990) An amino-terminal fragment of urokinase isolated from a prostate cancer cell line (PC-3) is mitogenic for osteoblast-such as cells. Biochem Biophys Res Commun 173(3):1058–1064PubMed
50.
go back to reference Christopherson KW 2nd, Hangoc G, Broxmeyer HE (2002) Cell surface peptidase CD26/dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1 alpha-mediated chemotaxis of human cord blood CD34+ progenitor cells. J Immunol 169(12):7000–7008PubMed Christopherson KW 2nd, Hangoc G, Broxmeyer HE (2002) Cell surface peptidase CD26/dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1 alpha-mediated chemotaxis of human cord blood CD34+ progenitor cells. J Immunol 169(12):7000–7008PubMed
51.
go back to reference Sun YX et al (2008) CD26/dipeptidyl peptidase IV regulates prostate cancer metastasis by degrading SDF-1/CXCL12. Clin Exp Metastasis 25(7):765–776PubMed Sun YX et al (2008) CD26/dipeptidyl peptidase IV regulates prostate cancer metastasis by degrading SDF-1/CXCL12. Clin Exp Metastasis 25(7):765–776PubMed
52.
go back to reference Christopherson KW 2nd et al (2004) Modulation of hematopoietic stem cell homing and engraftment by CD26. Science 305(5686):1000–1003PubMed Christopherson KW 2nd et al (2004) Modulation of hematopoietic stem cell homing and engraftment by CD26. Science 305(5686):1000–1003PubMed
53.
go back to reference Cramer SD, Chen Z, Peehl DM (1996) Prostate specific antigen cleaves parathyroid hormone-related protein in the PTH-such as domain: inactivation of PTHrP-stimulated cAMP accumulation in mouse osteoblasts. J Urol 156(2 Pt 1):526–531PubMed Cramer SD, Chen Z, Peehl DM (1996) Prostate specific antigen cleaves parathyroid hormone-related protein in the PTH-such as domain: inactivation of PTHrP-stimulated cAMP accumulation in mouse osteoblasts. J Urol 156(2 Pt 1):526–531PubMed
54.
go back to reference Dallas SL et al (1995) Dual role for the latent transforming growth factor-beta binding protein in storage of latent TGF-beta in the extracellular matrix and as a structural matrix protein. J Cell Biol 131(2):539–549PubMed Dallas SL et al (1995) Dual role for the latent transforming growth factor-beta binding protein in storage of latent TGF-beta in the extracellular matrix and as a structural matrix protein. J Cell Biol 131(2):539–549PubMed
55.
go back to reference Iwamura M et al (1996) Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen. Urology 48(2):317–325PubMed Iwamura M et al (1996) Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen. Urology 48(2):317–325PubMed
56.
go back to reference Killian CS et al (1993) Mitogenic response of osteoblast cells to prostate-specific antigen suggests an activation of latent TGF-beta and a proteolytic modulation of cell adhesion receptors. Biochem Biophys Res Commun 192(2):940–947PubMed Killian CS et al (1993) Mitogenic response of osteoblast cells to prostate-specific antigen suggests an activation of latent TGF-beta and a proteolytic modulation of cell adhesion receptors. Biochem Biophys Res Commun 192(2):940–947PubMed
57.
go back to reference Nadiminty N et al (2006) Prostate-specific antigen modulates genes involved in bone remodeling and induces osteoblast differentiation of human osteosarcoma cell line SaOS-2. Clin Cancer Res 12(5):1420–1430PubMed Nadiminty N et al (2006) Prostate-specific antigen modulates genes involved in bone remodeling and induces osteoblast differentiation of human osteosarcoma cell line SaOS-2. Clin Cancer Res 12(5):1420–1430PubMed
58.
go back to reference Nagasawa T, Tachibana K, Kishimoto T (1998) A novel CXC chemokine PBSF/SDF-1 and its receptor CXCR4: their functions in development, hematopoiesis and HIV infection. Semin Immunol 10(3):179–185PubMed Nagasawa T, Tachibana K, Kishimoto T (1998) A novel CXC chemokine PBSF/SDF-1 and its receptor CXCR4: their functions in development, hematopoiesis and HIV infection. Semin Immunol 10(3):179–185PubMed
59.
go back to reference Ponomaryov T et al (2000) Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function. J Clin Invest 106(11):1331–1339PubMed Ponomaryov T et al (2000) Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function. J Clin Invest 106(11):1331–1339PubMed
60.
go back to reference Loetscher M et al (1994) Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem 269(1):232–237PubMed Loetscher M et al (1994) Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem 269(1):232–237PubMed
61.
go back to reference Peled A et al (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283(5403):845–848PubMed Peled A et al (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283(5403):845–848PubMed
62.
go back to reference Kollet O et al (2001) Rapid and efficient homing of human CD34(+)CD38(−/low)CXCR4(+) stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null) mice. Blood 97(10):3283–3291PubMed Kollet O et al (2001) Rapid and efficient homing of human CD34(+)CD38(−/low)CXCR4(+) stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null) mice. Blood 97(10):3283–3291PubMed
63.
go back to reference Peled A et al (1999) The chemokine SDF-1 stimulates integrin-mediated arrest of CD34(+) cells on vascular endothelium under shear flow. J Clin Invest 104(9):1199–1211PubMed Peled A et al (1999) The chemokine SDF-1 stimulates integrin-mediated arrest of CD34(+) cells on vascular endothelium under shear flow. J Clin Invest 104(9):1199–1211PubMed
64.
go back to reference Peled A et al (2000) The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 95(11):3289–3296PubMed Peled A et al (2000) The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 95(11):3289–3296PubMed
65.
go back to reference Wysoczynski M et al (2005) Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient. Blood 105(1):40–48PubMed Wysoczynski M et al (2005) Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient. Blood 105(1):40–48PubMed
66.
go back to reference Taichman RS et al (2002) Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res 62(6):1832–1837PubMed Taichman RS et al (2002) Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res 62(6):1832–1837PubMed
67.
go back to reference Sun YX et al (2005) Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. J Bone Miner Res 20(2):318–329PubMed Sun YX et al (2005) Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. J Bone Miner Res 20(2):318–329PubMed
68.
go back to reference Sun YX et al (2003) Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo. J Cell Biochem 89(3):462–473PubMed Sun YX et al (2003) Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo. J Cell Biochem 89(3):462–473PubMed
69.
go back to reference Arya M et al (2004) The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis. J Exp Ther Oncol 4(4):291–303PubMed Arya M et al (2004) The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis. J Exp Ther Oncol 4(4):291–303PubMed
70.
go back to reference Wang J et al (2008) The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem 283(7):4283–4294PubMed Wang J et al (2008) The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem 283(7):4283–4294PubMed
71.
go back to reference Muller A et al (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410(6824):50–56PubMed Muller A et al (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410(6824):50–56PubMed
72.
go back to reference Sloan EK, Anderson RL (2002) Genes involved in breast cancer metastasis to bone. Cell Mol Life Sci 59(9):1491–1502PubMed Sloan EK, Anderson RL (2002) Genes involved in breast cancer metastasis to bone. Cell Mol Life Sci 59(9):1491–1502PubMed
73.
go back to reference Kang Y et al (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3(6):537–549PubMed Kang Y et al (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3(6):537–549PubMed
74.
go back to reference Luker KE, Luker GD (2006) Functions of CXCL12 and CXCR4 in breast cancer. Cancer Lett 238(1):30–41PubMed Luker KE, Luker GD (2006) Functions of CXCL12 and CXCR4 in breast cancer. Cancer Lett 238(1):30–41PubMed
75.
go back to reference Shim H et al (2006) Lower expression of CXCR4 in lymph node metastases than in primary breast cancers: potential regulation by ligand-dependent degradation and HIF-1alpha. Biochem Biophys Res Commun 346(1):252–258PubMed Shim H et al (2006) Lower expression of CXCR4 in lymph node metastases than in primary breast cancers: potential regulation by ligand-dependent degradation and HIF-1alpha. Biochem Biophys Res Commun 346(1):252–258PubMed
76.
go back to reference Salvucci O et al (2006) The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study. Breast Cancer Res Treat 97(3):275–283PubMed Salvucci O et al (2006) The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study. Breast Cancer Res Treat 97(3):275–283PubMed
77.
go back to reference Bradstock KF et al (2000) Effects of the chemokine stromal cell-derived factor-1 on the migration and localization of precursor-B acute lymphoblastic leukemia cells within bone marrow stromal layers. Leukemia 14(5):882–888PubMed Bradstock KF et al (2000) Effects of the chemokine stromal cell-derived factor-1 on the migration and localization of precursor-B acute lymphoblastic leukemia cells within bone marrow stromal layers. Leukemia 14(5):882–888PubMed
78.
go back to reference Bendall LJ et al (2005) Defective p38 mitogen-activated protein kinase signaling impairs chemotaxic but not proliferative responses to stromal-derived factor-1alpha in acute lymphoblastic leukemia. Cancer Res 65(8):3290–3298PubMed Bendall LJ et al (2005) Defective p38 mitogen-activated protein kinase signaling impairs chemotaxic but not proliferative responses to stromal-derived factor-1alpha in acute lymphoblastic leukemia. Cancer Res 65(8):3290–3298PubMed
79.
go back to reference Spiegel A et al (2004) Unique SDF-1-induced activation of human precursor-B ALL cells as a result of altered CXCR4 expression and signaling. Blood 103(8):2900–2907PubMed Spiegel A et al (2004) Unique SDF-1-induced activation of human precursor-B ALL cells as a result of altered CXCR4 expression and signaling. Blood 103(8):2900–2907PubMed
80.
go back to reference Mohle R et al (1998) The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1. Blood 91(12):4523–4530PubMed Mohle R et al (1998) The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1. Blood 91(12):4523–4530PubMed
81.
go back to reference Voermans C et al (2002) Migratory behavior of leukemic cells from acute myeloid leukemia patients. Leukemia 16(4):650–657PubMed Voermans C et al (2002) Migratory behavior of leukemic cells from acute myeloid leukemia patients. Leukemia 16(4):650–657PubMed
82.
go back to reference Burger JA et al (2003) CXCR4 chemokine receptors (CD184) and alpha4beta1 integrins mediate spontaneous migration of human CD34+ progenitors and acute myeloid leukaemia cells beneath marrow stromal cells (pseudoemperipolesis). Br J Haematol 122(4):579–589PubMed Burger JA et al (2003) CXCR4 chemokine receptors (CD184) and alpha4beta1 integrins mediate spontaneous migration of human CD34+ progenitors and acute myeloid leukaemia cells beneath marrow stromal cells (pseudoemperipolesis). Br J Haematol 122(4):579–589PubMed
83.
go back to reference Tavor S et al (2004) CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. Cancer Res 64(8):2817–2824PubMed Tavor S et al (2004) CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. Cancer Res 64(8):2817–2824PubMed
84.
go back to reference Monaco G et al (2004) Engraftment of acute myeloid leukemia in NOD/SCID mice is independent of CXCR4 and predicts poor patient survival. Stem Cells 22(2):188–201PubMed Monaco G et al (2004) Engraftment of acute myeloid leukemia in NOD/SCID mice is independent of CXCR4 and predicts poor patient survival. Stem Cells 22(2):188–201PubMed
85.
go back to reference Burger JA, Burger M, Kipps TJ (1999) Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells. Blood 94(11):3658–3667PubMed Burger JA, Burger M, Kipps TJ (1999) Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells. Blood 94(11):3658–3667PubMed
86.
go back to reference Burger M et al (2005) Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells. Blood 106(5):1824–1830PubMed Burger M et al (2005) Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells. Blood 106(5):1824–1830PubMed
87.
go back to reference Lu Y et al (2008) CXCL16 functions as a novel chemotactic factor for prostate cancer cells in vitro. Mol Cancer Res 6(4):546–554PubMed Lu Y et al (2008) CXCL16 functions as a novel chemotactic factor for prostate cancer cells in vitro. Mol Cancer Res 6(4):546–554PubMed
88.
go back to reference Takahashi S et al (1994) Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption. J Biol Chem 269(46):28696–28701PubMed Takahashi S et al (1994) Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption. J Biol Chem 269(46):28696–28701PubMed
89.
go back to reference Jung Y et al (2007) Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood 110(1):82–90PubMed Jung Y et al (2007) Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood 110(1):82–90PubMed
90.
go back to reference Cole SP et al (1992) Elevated expression of annexin II (lipocortin II, p36) in a multidrug resistant small cell lung cancer cell line. Br J Cancer 65(4):498–502PubMed Cole SP et al (1992) Elevated expression of annexin II (lipocortin II, p36) in a multidrug resistant small cell lung cancer cell line. Br J Cancer 65(4):498–502PubMed
91.
go back to reference Emoto K et al (2001) Annexin II overexpression correlates with stromal tenascin-C overexpression: a prognostic marker in colorectal carcinoma. Cancer 92(6):1419–1426PubMed Emoto K et al (2001) Annexin II overexpression correlates with stromal tenascin-C overexpression: a prognostic marker in colorectal carcinoma. Cancer 92(6):1419–1426PubMed
92.
go back to reference Roseman BJ et al (1994) Annexin II marks astrocytic brain tumors of high histologic grade. Oncol Res 6(12):561–567PubMed Roseman BJ et al (1994) Annexin II marks astrocytic brain tumors of high histologic grade. Oncol Res 6(12):561–567PubMed
93.
go back to reference Vishwanatha JK et al (1993) Enhanced expression of annexin II in human pancreatic carcinoma cells and primary pancreatic cancers. Carcinogenesis 14(12):2575–2579PubMed Vishwanatha JK et al (1993) Enhanced expression of annexin II in human pancreatic carcinoma cells and primary pancreatic cancers. Carcinogenesis 14(12):2575–2579PubMed
94.
go back to reference Shiozawa Y et al (2008) Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer. J Cell Biochem 105(2):370–380PubMed Shiozawa Y et al (2008) Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer. J Cell Biochem 105(2):370–380PubMed
95.
go back to reference Shiozawa Y, Pedersen EA, Taichman RS (2010) GAS6/Mer axis regulates the homing and survival of the E2A/PBX1-positive B-cell precursor acute lymphoblastic leukemia in the bone marrow niche. Exp Hematol 38(2):132–140PubMed Shiozawa Y, Pedersen EA, Taichman RS (2010) GAS6/Mer axis regulates the homing and survival of the E2A/PBX1-positive B-cell precursor acute lymphoblastic leukemia in the bone marrow niche. Exp Hematol 38(2):132–140PubMed
96.
go back to reference Gjerdrum C et al (2010) Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc Natl Acad Sci USA 107(3):1124–1129PubMed Gjerdrum C et al (2010) Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc Natl Acad Sci USA 107(3):1124–1129PubMed
97.
go back to reference Koorstra JB et al (2009) The Axl receptor tyrosine kinase confers an adverse prognostic influence in pancreatic cancer and represents a new therapeutic target. Cancer Biol Ther 8(7):618–626PubMed Koorstra JB et al (2009) The Axl receptor tyrosine kinase confers an adverse prognostic influence in pancreatic cancer and represents a new therapeutic target. Cancer Biol Ther 8(7):618–626PubMed
98.
go back to reference Rankin EB et al (2010) AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res 70(19):7570–7579PubMed Rankin EB et al (2010) AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res 70(19):7570–7579PubMed
99.
go back to reference Hector A et al (2010) The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer Biol Ther 10(10):1009–1018PubMed Hector A et al (2010) The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer Biol Ther 10(10):1009–1018PubMed
100.
go back to reference Gustafsson A et al (2009) Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma. PLoS One 4(10):e7575PubMed Gustafsson A et al (2009) Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma. PLoS One 4(10):e7575PubMed
101.
go back to reference Shiozawa Y et al (2010) GAS6/AXL axis regulates prostate cancer invasion, proliferation, and survival in the bone marrow niche. Neoplasia 12(2):116–127PubMed Shiozawa Y et al (2010) GAS6/AXL axis regulates prostate cancer invasion, proliferation, and survival in the bone marrow niche. Neoplasia 12(2):116–127PubMed
102.
go back to reference Hill A et al (2006) The emerging role of CD44 in regulating skeletal micrometastasis. Cancer Lett 237(1):1–9PubMed Hill A et al (2006) The emerging role of CD44 in regulating skeletal micrometastasis. Cancer Lett 237(1):1–9PubMed
103.
go back to reference Avigdor A et al (2004) CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood 103(8):2981–2989PubMed Avigdor A et al (2004) CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood 103(8):2981–2989PubMed
104.
go back to reference Nilsson SK et al (2005) Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 106(4):1232–1239PubMed Nilsson SK et al (2005) Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 106(4):1232–1239PubMed
105.
go back to reference Fedarko NS et al (2001) Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer. Clin Cancer Res 7(12):4060–4066PubMed Fedarko NS et al (2001) Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer. Clin Cancer Res 7(12):4060–4066PubMed
106.
go back to reference Rudland PS et al (2002) Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res 62(12):3417–3427PubMed Rudland PS et al (2002) Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res 62(12):3417–3427PubMed
107.
go back to reference Thalmann GN et al (1999) Osteopontin: possible role in prostate cancer progression. Clin Cancer Res 5(8):2271–2277PubMed Thalmann GN et al (1999) Osteopontin: possible role in prostate cancer progression. Clin Cancer Res 5(8):2271–2277PubMed
108.
go back to reference Tuck AB et al (1997) Osteopontin and p53 expression are associated with tumor progression in a case of synchronous, bilateral, invasive mammary carcinomas. Arch Pathol Lab Med 121(6):578–584PubMed Tuck AB et al (1997) Osteopontin and p53 expression are associated with tumor progression in a case of synchronous, bilateral, invasive mammary carcinomas. Arch Pathol Lab Med 121(6):578–584PubMed
109.
go back to reference Tuck AB et al (1999) Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells. Oncogene 18(29):4237–4246PubMed Tuck AB et al (1999) Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells. Oncogene 18(29):4237–4246PubMed
110.
go back to reference Wai PY, Kuo PC (2004) The role of Osteopontin in tumor metastasis. J Surg Res 121(2):228–241PubMed Wai PY, Kuo PC (2004) The role of Osteopontin in tumor metastasis. J Surg Res 121(2):228–241PubMed
111.
go back to reference Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285(5430):1028–1032PubMed Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285(5430):1028–1032PubMed
112.
go back to reference Furger KA et al (2003) Beta(3) integrin expression increases breast carcinoma cell responsiveness to the malignancy-enhancing effects of osteopontin. Mol Cancer Res 1(11):810–819PubMed Furger KA et al (2003) Beta(3) integrin expression increases breast carcinoma cell responsiveness to the malignancy-enhancing effects of osteopontin. Mol Cancer Res 1(11):810–819PubMed
113.
go back to reference Sun YX et al (2007) Expression and activation of alpha v beta 3 integrins by SDF-1/CXC12 increases the aggressiveness of prostate cancer cells. Prostate 67(1):61–73PubMed Sun YX et al (2007) Expression and activation of alpha v beta 3 integrins by SDF-1/CXC12 increases the aggressiveness of prostate cancer cells. Prostate 67(1):61–73PubMed
114.
go back to reference Sethi T et al (1999) Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat Med 5(6):662–668PubMed Sethi T et al (1999) Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat Med 5(6):662–668PubMed
115.
go back to reference Hodkinson PS et al (2006) ECM overrides DNA damage-induced cell cycle arrest and apoptosis in small-cell lung cancer cells through beta1 integrin-dependent activation of PI3-kinase. Cell Death Differ 13(10):1776–1788PubMed Hodkinson PS et al (2006) ECM overrides DNA damage-induced cell cycle arrest and apoptosis in small-cell lung cancer cells through beta1 integrin-dependent activation of PI3-kinase. Cell Death Differ 13(10):1776–1788PubMed
116.
go back to reference Aoudjit F, Vuori K (2001) Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells. Oncogene 20(36):4995–5004PubMed Aoudjit F, Vuori K (2001) Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells. Oncogene 20(36):4995–5004PubMed
117.
go back to reference Matsunaga T et al (2003) Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat Med 9(9):1158–1165PubMed Matsunaga T et al (2003) Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat Med 9(9):1158–1165PubMed
118.
go back to reference Verfaillie CM (1998) Adhesion receptors as regulators of the hematopoietic process. Blood 92(8):2609–2612PubMed Verfaillie CM (1998) Adhesion receptors as regulators of the hematopoietic process. Blood 92(8):2609–2612PubMed
119.
go back to reference Taichman RS (2005) Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 105(7):2631–2639PubMed Taichman RS (2005) Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 105(7):2631–2639PubMed
120.
go back to reference Chu K et al (2008) Cadherin-11 promotes the metastasis of prostate cancer cells to bone. Mol Cancer Res 6(8):1259–1267PubMed Chu K et al (2008) Cadherin-11 promotes the metastasis of prostate cancer cells to bone. Mol Cancer Res 6(8):1259–1267PubMed
121.
go back to reference Huang CF et al (2010) Cadherin-11 increases migration and invasion of prostate cancer cells and enhances their interaction with osteoblasts. Cancer Res 70(11):4580–4589PubMed Huang CF et al (2010) Cadherin-11 increases migration and invasion of prostate cancer cells and enhances their interaction with osteoblasts. Cancer Res 70(11):4580–4589PubMed
122.
go back to reference Tamura D et al (2008) Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone. Int J Oncol 33(1):17–24PubMed Tamura D et al (2008) Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone. Int J Oncol 33(1):17–24PubMed
123.
go back to reference Wein F et al (2010) N-cadherin is expressed on human hematopoietic progenitor cells and mediates interaction with human mesenchymal stromal cells. Stem Cell Res 4(2):129–139PubMed Wein F et al (2010) N-cadherin is expressed on human hematopoietic progenitor cells and mediates interaction with human mesenchymal stromal cells. Stem Cell Res 4(2):129–139PubMed
124.
go back to reference Kiel MJ et al (2009) Hematopoietic stem cells do not depend on N-cadherin to regulate their maintenance. Cell Stem Cell 4(2):170–179PubMed Kiel MJ et al (2009) Hematopoietic stem cells do not depend on N-cadherin to regulate their maintenance. Cell Stem Cell 4(2):170–179PubMed
125.
go back to reference Fidler IJ, Kim S-J, Langley RR (2007) The role of the organ microenvironment in the biology and therapy of cancer metastasis. J Cell Biochem 101(4):927–936PubMed Fidler IJ, Kim S-J, Langley RR (2007) The role of the organ microenvironment in the biology and therapy of cancer metastasis. J Cell Biochem 101(4):927–936PubMed
126.
go back to reference Yoneda T, Hiraga T (2005) Crosstalk between cancer cells and bone microenvironment in bone metastasis. Biochem Biophys Res Commun 328(3):679–687PubMed Yoneda T, Hiraga T (2005) Crosstalk between cancer cells and bone microenvironment in bone metastasis. Biochem Biophys Res Commun 328(3):679–687PubMed
127.
go back to reference Lacey DL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93(2):165–176PubMed Lacey DL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93(2):165–176PubMed
128.
go back to reference Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337–342PubMed Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337–342PubMed
129.
go back to reference Simonet WS et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89(2):309–319PubMed Simonet WS et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89(2):309–319PubMed
130.
go back to reference Grimaud E et al (2003) Receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio is increased in severe osteolysis. Am J Pathol 163(5):2021–2031PubMed Grimaud E et al (2003) Receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio is increased in severe osteolysis. Am J Pathol 163(5):2021–2031PubMed
131.
go back to reference Brown JM et al (2001) Osteoprotegerin and rank ligand expression in prostate cancer. Urology 57(4):611–616PubMed Brown JM et al (2001) Osteoprotegerin and rank ligand expression in prostate cancer. Urology 57(4):611–616PubMed
132.
go back to reference Lynch CC et al (2005) MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell 7(5):485–496PubMed Lynch CC et al (2005) MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell 7(5):485–496PubMed
133.
go back to reference Sordillo EM, Pearse RN (2003) RANK-Fc: a therapeutic antagonist for RANK-L in myeloma. Cancer 97(3 Suppl):802–812PubMed Sordillo EM, Pearse RN (2003) RANK-Fc: a therapeutic antagonist for RANK-L in myeloma. Cancer 97(3 Suppl):802–812PubMed
134.
go back to reference Jones DH et al (2006) Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440(7084):692–696PubMed Jones DH et al (2006) Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440(7084):692–696PubMed
135.
go back to reference Miller J et al (2002) The core-binding factor beta subunit is required for bone formation and hematopoietic maturation. Nat Genet 32(4):645–649PubMed Miller J et al (2002) The core-binding factor beta subunit is required for bone formation and hematopoietic maturation. Nat Genet 32(4):645–649PubMed
136.
go back to reference Komori T et al (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89(5):755–764PubMed Komori T et al (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89(5):755–764PubMed
137.
go back to reference Barnes GL et al (2003) Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells. Cancer Res 63(10):2631–2637PubMed Barnes GL et al (2003) Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells. Cancer Res 63(10):2631–2637PubMed
138.
go back to reference Enomoto H et al (2003) Induction of osteoclast differentiation by Runx2 through receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin regulation and partial rescue of osteoclastogenesis in Runx2-/- mice by RANKL transgene. J Biol Chem 278(26):23971–23977PubMed Enomoto H et al (2003) Induction of osteoclast differentiation by Runx2 through receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin regulation and partial rescue of osteoclastogenesis in Runx2-/- mice by RANKL transgene. J Biol Chem 278(26):23971–23977PubMed
139.
go back to reference Pratap J et al (2005) The Runx2 osteogenic transcription factor regulates matrix metalloproteinase 9 in bone metastatic cancer cells and controls cell invasion. Mol Cell Biol 25(19):8581–8591PubMed Pratap J et al (2005) The Runx2 osteogenic transcription factor regulates matrix metalloproteinase 9 in bone metastatic cancer cells and controls cell invasion. Mol Cell Biol 25(19):8581–8591PubMed
140.
go back to reference Pratap J et al (2006) Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. Cancer Metastasis Rev 25(4):589–600PubMed Pratap J et al (2006) Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. Cancer Metastasis Rev 25(4):589–600PubMed
141.
go back to reference Akech J et al (2010) Runx2 association with progression of prostate cancer in patients: mechanisms mediating bone osteolysis and osteoblastic metastatic lesions. Oncogene 29(6):811–821PubMed Akech J et al (2010) Runx2 association with progression of prostate cancer in patients: mechanisms mediating bone osteolysis and osteoblastic metastatic lesions. Oncogene 29(6):811–821PubMed
142.
go back to reference Baniwal SK et al (2010) Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis. Mol Cancer 9:258PubMed Baniwal SK et al (2010) Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis. Mol Cancer 9:258PubMed
143.
go back to reference Elliott RL, Blobe GC (2005) Role of transforming growth factor Beta in human cancer. J Clin Oncol 23(9):2078–2093PubMed Elliott RL, Blobe GC (2005) Role of transforming growth factor Beta in human cancer. J Clin Oncol 23(9):2078–2093PubMed
144.
go back to reference Mohammad KS et al (2009) Pharmacologic inhibition of the TGF-beta type I receptor kinase has anabolic and anti-catabolic effects on bone. PLoS One 4(4):e5275PubMed Mohammad KS et al (2009) Pharmacologic inhibition of the TGF-beta type I receptor kinase has anabolic and anti-catabolic effects on bone. PLoS One 4(4):e5275PubMed
145.
go back to reference Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425(6958):577–584PubMed Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425(6958):577–584PubMed
146.
go back to reference Massague J (2000) How cells read TGF-beta signals. Nat Rev Mol Cell Biol 1(3):169–178PubMed Massague J (2000) How cells read TGF-beta signals. Nat Rev Mol Cell Biol 1(3):169–178PubMed
147.
go back to reference Dallas SL et al (2002) Proteolysis of latent transforming growth factor-beta (TGF-beta)-binding protein-1 by osteoclasts. A cellular mechanism for release of TGF-beta from bone matrix. J Biol Chem 277(24):21352–21360PubMed Dallas SL et al (2002) Proteolysis of latent transforming growth factor-beta (TGF-beta)-binding protein-1 by osteoclasts. A cellular mechanism for release of TGF-beta from bone matrix. J Biol Chem 277(24):21352–21360PubMed
148.
go back to reference Kakonen SM et al (2002) Transforming growth factor-beta stimulates parathyroid hormone-related protein and osteolytic metastases via Smad and mitogen-activated protein kinase signaling pathways. J Biol Chem 277(27):24571–24578PubMed Kakonen SM et al (2002) Transforming growth factor-beta stimulates parathyroid hormone-related protein and osteolytic metastases via Smad and mitogen-activated protein kinase signaling pathways. J Biol Chem 277(27):24571–24578PubMed
149.
go back to reference Kitazawa S, Kitazawa R (2002) RANK ligand is a prerequisite for cancer-associated osteolytic lesions. J Pathol 198(2):228–236PubMed Kitazawa S, Kitazawa R (2002) RANK ligand is a prerequisite for cancer-associated osteolytic lesions. J Pathol 198(2):228–236PubMed
150.
go back to reference Kondo H, Guo J, Bringhurst FR (2002) Cyclic adenosine monophosphate/protein kinase A mediates parathyroid hormone/parathyroid hormone-related protein receptor regulation of osteoclastogenesis and expression of RANKL and osteoprotegerin mRNAs by marrow stromal cells. J Bone Miner Res 17(9):1667–1679PubMed Kondo H, Guo J, Bringhurst FR (2002) Cyclic adenosine monophosphate/protein kinase A mediates parathyroid hormone/parathyroid hormone-related protein receptor regulation of osteoclastogenesis and expression of RANKL and osteoprotegerin mRNAs by marrow stromal cells. J Bone Miner Res 17(9):1667–1679PubMed
151.
go back to reference Gallwitz WE, Guise TA, Mundy GR (2002) Guanosine nucleotides inhibit different syndromes of PTHrP excess caused by human cancers in vivo. J Clin Invest 110(10):1559–1572PubMed Gallwitz WE, Guise TA, Mundy GR (2002) Guanosine nucleotides inhibit different syndromes of PTHrP excess caused by human cancers in vivo. J Clin Invest 110(10):1559–1572PubMed
152.
go back to reference Javelaud D et al (2007) Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. Cancer Res 67(5):2317–2324PubMed Javelaud D et al (2007) Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. Cancer Res 67(5):2317–2324PubMed
153.
go back to reference Alexaki VI et al (2010) GLI2-mediated melanoma invasion and metastasis. J Natl Cancer Inst 102(15):1148–1159PubMed Alexaki VI et al (2010) GLI2-mediated melanoma invasion and metastasis. J Natl Cancer Inst 102(15):1148–1159PubMed
154.
go back to reference Gazzerro E, Canalis E (2006) Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord 7(1–2):51–65PubMed Gazzerro E, Canalis E (2006) Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord 7(1–2):51–65PubMed
155.
go back to reference Katsuno Y et al (2008) Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway. Oncogene 27(49):6322–6333PubMed Katsuno Y et al (2008) Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway. Oncogene 27(49):6322–6333PubMed
156.
go back to reference Lai TH et al (2008) Osteoblasts-derived BMP-2 enhances the motility of prostate cancer cells via activation of integrins. Prostate 68(12):1341–1353PubMed Lai TH et al (2008) Osteoblasts-derived BMP-2 enhances the motility of prostate cancer cells via activation of integrins. Prostate 68(12):1341–1353PubMed
157.
go back to reference Virk MS et al (2009) Influence of simultaneous targeting of the bone morphogenetic protein pathway and RANK/RANKL axis in osteolytic prostate cancer lesion in bone. Bone 44(1):160–167PubMed Virk MS et al (2009) Influence of simultaneous targeting of the bone morphogenetic protein pathway and RANK/RANKL axis in osteolytic prostate cancer lesion in bone. Bone 44(1):160–167PubMed
158.
go back to reference Hauschka PV et al (1986) Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose. J Biol Chem 261(27):12665–12674PubMed Hauschka PV et al (1986) Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose. J Biol Chem 261(27):12665–12674PubMed
159.
go back to reference Goya M et al (2004) Growth inhibition of human prostate cancer cells in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice by a ligand-specific antibody to human insulin-such as growth factors. Cancer Res 64(17):6252–6258PubMed Goya M et al (2004) Growth inhibition of human prostate cancer cells in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice by a ligand-specific antibody to human insulin-such as growth factors. Cancer Res 64(17):6252–6258PubMed
160.
go back to reference van Golen CM et al (2006) Insulin-such as growth factor-I receptor expression regulates neuroblastoma metastasis to bone. Cancer Res 66(13):6570–6578PubMed van Golen CM et al (2006) Insulin-such as growth factor-I receptor expression regulates neuroblastoma metastasis to bone. Cancer Res 66(13):6570–6578PubMed
161.
go back to reference Kingsley LA et al (2007) Molecular biology of bone metastasis. Mol Cancer Ther 6(10):2609–2617PubMed Kingsley LA et al (2007) Molecular biology of bone metastasis. Mol Cancer Ther 6(10):2609–2617PubMed
162.
go back to reference Zhong H et al (1999) Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 59(22):5830–5835PubMed Zhong H et al (1999) Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 59(22):5830–5835PubMed
163.
go back to reference Le QT, Denko NC, Giaccia AJ (2004) Hypoxic gene expression and metastasis. Cancer Metastasis Rev 23(3–4):293–310PubMed Le QT, Denko NC, Giaccia AJ (2004) Hypoxic gene expression and metastasis. Cancer Metastasis Rev 23(3–4):293–310PubMed
164.
go back to reference Garayoa M et al (2000) Hypoxia-inducible factor-1 (HIF-1) up-regulates adrenomedullin expression in human tumor cell lines during oxygen deprivation: a possible promotion mechanism of carcinogenesis. Mol Endocrinol 14(6):848–862PubMed Garayoa M et al (2000) Hypoxia-inducible factor-1 (HIF-1) up-regulates adrenomedullin expression in human tumor cell lines during oxygen deprivation: a possible promotion mechanism of carcinogenesis. Mol Endocrinol 14(6):848–862PubMed
165.
go back to reference McMahon S et al (2006) Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression. J Biol Chem 281(34):24171–24181PubMed McMahon S et al (2006) Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression. J Biol Chem 281(34):24171–24181PubMed
166.
go back to reference Hiraga T et al (2007) Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone metastases of breast cancer. Cancer Res 67(9):4157–4163PubMed Hiraga T et al (2007) Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone metastases of breast cancer. Cancer Res 67(9):4157–4163PubMed
167.
go back to reference Brandao-Burch A et al (2005) Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization. Calcif Tissue Int 77(3):167–174PubMed Brandao-Burch A et al (2005) Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization. Calcif Tissue Int 77(3):167–174PubMed
168.
go back to reference Webb SD, Sherratt JA, Fish RG (1999) Alterations in proteolytic activity at low pH and its association with invasion: a theoretical model. Clin Exp Metastasis 17(5):397–407PubMed Webb SD, Sherratt JA, Fish RG (1999) Alterations in proteolytic activity at low pH and its association with invasion: a theoretical model. Clin Exp Metastasis 17(5):397–407PubMed
169.
go back to reference Shannon AM et al (2003) Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev 29(4):297–307PubMed Shannon AM et al (2003) Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev 29(4):297–307PubMed
170.
go back to reference Berger CE et al (2001) Scanning electrochemical microscopy at the surface of bone-resorbing osteoclasts: evidence for steady-state disposal and intracellular functional compartmentalization of calcium. J Bone Miner Res 16(11):2092–2102PubMed Berger CE et al (2001) Scanning electrochemical microscopy at the surface of bone-resorbing osteoclasts: evidence for steady-state disposal and intracellular functional compartmentalization of calcium. J Bone Miner Res 16(11):2092–2102PubMed
171.
go back to reference Chattopadhyay N (2006) Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy. Am J Physiol Endocrinol Metab 290(5):E761–E770PubMed Chattopadhyay N (2006) Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy. Am J Physiol Endocrinol Metab 290(5):E761–E770PubMed
172.
go back to reference Sanders JL et al (2000) Extracellular calcium-sensing receptor expression and its potential role in regulating parathyroid hormone-related peptide secretion in human breast cancer cell lines. Endocrinology 141(12):4357–4364PubMed Sanders JL et al (2000) Extracellular calcium-sensing receptor expression and its potential role in regulating parathyroid hormone-related peptide secretion in human breast cancer cell lines. Endocrinology 141(12):4357–4364PubMed
173.
go back to reference Sanders JL et al (2001) Ca(2+)-sensing receptor expression and PTHrP secretion in PC-3 human prostate cancer cells. Am J Physiol Endocrinol Metab 281(6):E1267–E1274PubMed Sanders JL et al (2001) Ca(2+)-sensing receptor expression and PTHrP secretion in PC-3 human prostate cancer cells. Am J Physiol Endocrinol Metab 281(6):E1267–E1274PubMed
174.
go back to reference Liao J et al (2006) Extracellular calcium as a candidate mediator of prostate cancer skeletal metastasis. Cancer Res 66(18):9065–9073PubMed Liao J et al (2006) Extracellular calcium as a candidate mediator of prostate cancer skeletal metastasis. Cancer Res 66(18):9065–9073PubMed
175.
go back to reference Mihai R et al (2006) Expression of the calcium receptor in human breast cancer–a potential new marker predicting the risk of bone metastases. Eur J Surg Oncol 32(5):511–515PubMed Mihai R et al (2006) Expression of the calcium receptor in human breast cancer–a potential new marker predicting the risk of bone metastases. Eur J Surg Oncol 32(5):511–515PubMed
176.
go back to reference Wilson A, Trumpp A (2006) Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 6(2):93–106PubMed Wilson A, Trumpp A (2006) Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 6(2):93–106PubMed
177.
go back to reference Yin T, Li L (2006) The stem cell niches in bone. J Clin Invest 116(5):1195–1201PubMed Yin T, Li L (2006) The stem cell niches in bone. J Clin Invest 116(5):1195–1201PubMed
178.
go back to reference Shiozawa Y, et al (2011) Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest 121(4):1298–1312 Shiozawa Y, et al (2011) Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest 121(4):1298–1312
179.
go back to reference Kaplan RN et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820–827PubMed Kaplan RN et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820–827PubMed
180.
go back to reference Roelofs AJ et al (2006) Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res 12(20 Pt 2):6222s–6230sPubMed Roelofs AJ et al (2006) Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res 12(20 Pt 2):6222s–6230sPubMed
181.
go back to reference Fizazi K et al (2009) Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol 27(10):1564–1571PubMed Fizazi K et al (2009) Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol 27(10):1564–1571PubMed
182.
go back to reference Mohammad KS et al (2011) TGF-beta-RI kinase inhibitor SD-208 reduces the development and progression of melanoma bone metastases. Cancer Res 71(1):175–184PubMed Mohammad KS et al (2011) TGF-beta-RI kinase inhibitor SD-208 reduces the development and progression of melanoma bone metastases. Cancer Res 71(1):175–184PubMed
183.
go back to reference Buijs JT et al (2007) BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am J Pathol 171(3):1047–1057PubMed Buijs JT et al (2007) BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am J Pathol 171(3):1047–1057PubMed
184.
go back to reference Coenegrachts L et al (2010) Anti-placental growth factor reduces bone metastasis by blocking tumor cell engraftment and osteoclast differentiation. Cancer Res 70(16):6537–6547PubMed Coenegrachts L et al (2010) Anti-placental growth factor reduces bone metastasis by blocking tumor cell engraftment and osteoclast differentiation. Cancer Res 70(16):6537–6547PubMed
185.
go back to reference Carducci MA, Jimeno A (2006) Targeting bone metastasis in prostate cancer with endothelin receptor antagonists. Clin Cancer Res 12(20 Pt 2):6296s–6300sPubMed Carducci MA, Jimeno A (2006) Targeting bone metastasis in prostate cancer with endothelin receptor antagonists. Clin Cancer Res 12(20 Pt 2):6296s–6300sPubMed
186.
go back to reference Zhao Y et al (2007) Tumor alphavbeta3 integrin is a therapeutic target for breast cancer bone metastases. Cancer Res 67(12):5821–5830PubMed Zhao Y et al (2007) Tumor alphavbeta3 integrin is a therapeutic target for breast cancer bone metastases. Cancer Res 67(12):5821–5830PubMed
187.
go back to reference Mori Y et al (2004) Anti-alpha4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis. Blood 104(7):2149–2154PubMed Mori Y et al (2004) Anti-alpha4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis. Blood 104(7):2149–2154PubMed
188.
go back to reference Petit I et al (2002) G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 3(7):687–694PubMed Petit I et al (2002) G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 3(7):687–694PubMed
189.
go back to reference Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home? Blood 106(6):1901–1910PubMed Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home? Blood 106(6):1901–1910PubMed
190.
go back to reference Abkowitz JL et al (2003) Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood 102(4):1249–1253PubMed Abkowitz JL et al (2003) Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood 102(4):1249–1253PubMed
191.
go back to reference Azab AK et al (2009) CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood 113(18):4341–4351PubMed Azab AK et al (2009) CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood 113(18):4341–4351PubMed
192.
go back to reference Nervi B et al (2009) Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood 113(24):6206–6214PubMed Nervi B et al (2009) Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood 113(24):6206–6214PubMed
193.
go back to reference Burger JA, Stewart DJ (2009) CXCR4 chemokine receptor antagonists: perspectives in SCLC. Expert Opin Investig Drugs 18(4):481–490PubMed Burger JA, Stewart DJ (2009) CXCR4 chemokine receptor antagonists: perspectives in SCLC. Expert Opin Investig Drugs 18(4):481–490PubMed
194.
go back to reference Hastie C et al (2008) Interferon-gamma reduces cell surface expression of annexin 2 and suppresses the invasive capacity of prostate cancer cells. J Biol Chem 283(18):12595–12603PubMed Hastie C et al (2008) Interferon-gamma reduces cell surface expression of annexin 2 and suppresses the invasive capacity of prostate cancer cells. J Biol Chem 283(18):12595–12603PubMed
Metadata
Title
Homing of Cancer Cells to the Bone
Authors
Anjali Mishra
Yusuke Shiozawa
Kenneth J. Pienta
Russell S. Taichman
Publication date
01-12-2011
Publisher
Springer Netherlands
Published in
Cancer Microenvironment / Issue 3/2011
Print ISSN: 1875-2292
Electronic ISSN: 1875-2284
DOI
https://doi.org/10.1007/s12307-011-0083-6

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