Skip to main content
Top
Published in: Molecular Cancer 1/2017

Open Access 01-12-2017 | Review

Mesenchymal stem cells: key players in cancer progression

Authors: Sarah M. Ridge, Francis J. Sullivan, Sharon A. Glynn

Published in: Molecular Cancer | Issue 1/2017

Login to get access

Abstract

Tumour progression is dependent on the interaction between tumour cells and cells of the surrounding microenvironment. The tumour is a dynamic milieu consisting of various cell types such as endothelial cells, fibroblasts, cells of the immune system and mesenchymal stem cells (MSCs). MSCs are multipotent stromal cells that are known to reside in various areas such as the bone marrow, fat and dental pulp. MSCs have been found to migrate towards inflammatory sites and studies have shown that they also migrate towards and incorporate into the tumour. The key question is how they interact there. MSCs may interact with tumour cells through paracrine signalling. On the other hand, MSCs have the capacity to differentiate to various cell types such as osteocytes, chondrocytes and adipocytes and it is possible that MSCs differentiate at the site of the tumour. More recently it has been shown that cross-talk between tumour cells and MSCs has been shown to increase metastatic potential and promote epithelial-to-mesenchymal transition. This review will focus on the role of MSCs in tumour development at various stages of progression from growth of the primary tumour to the establishment of distant metastasis.
Literature
1.
go back to reference Pietras K, Ostman A. Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res. 2010;316(8):1324–31.PubMedCrossRef Pietras K, Ostman A. Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res. 2010;316(8):1324–31.PubMedCrossRef
3.
go back to reference Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4(1):71–8.PubMedCrossRef Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4(1):71–8.PubMedCrossRef
4.
go back to reference Hall B, Andreeff M, Marini F. The participation of mesenchymal stem cells in tumor stroma formation and their application as targeted-gene delivery vehicles. Handb Exp Pharmacol. 2007;180:263–83.CrossRef Hall B, Andreeff M, Marini F. The participation of mesenchymal stem cells in tumor stroma formation and their application as targeted-gene delivery vehicles. Handb Exp Pharmacol. 2007;180:263–83.CrossRef
5.
go back to reference Young MR, Wright MA. Myelopoiesis-associated immune suppressor cells in mice bearing metastatic Lewis lung carcinoma tumors: gamma interferon plus tumor necrosis factor alpha synergistically reduces immune suppressor and tumor growth-promoting activities of bone marrow cells and diminishes tumor recurrence and metastasis. Cancer Res. 1992;52(22):6335–40.PubMed Young MR, Wright MA. Myelopoiesis-associated immune suppressor cells in mice bearing metastatic Lewis lung carcinoma tumors: gamma interferon plus tumor necrosis factor alpha synergistically reduces immune suppressor and tumor growth-promoting activities of bone marrow cells and diminishes tumor recurrence and metastasis. Cancer Res. 1992;52(22):6335–40.PubMed
6.
go back to reference Sato T, et al. Tumor-stromal cell contact promotes invasion of human uterine cervical carcinoma cells by augmenting the expression and activation of stromal matrix metalloproteinases. Gynecol Oncol. 2004;92(1):47–56.PubMedCrossRef Sato T, et al. Tumor-stromal cell contact promotes invasion of human uterine cervical carcinoma cells by augmenting the expression and activation of stromal matrix metalloproteinases. Gynecol Oncol. 2004;92(1):47–56.PubMedCrossRef
7.
go back to reference Sung SY, et al. Coevolution of prostate cancer and bone stroma in three-dimensional coculture: implications for cancer growth and metastasis. Cancer Res. 2008;68(23):9996–10003.PubMedPubMedCentralCrossRef Sung SY, et al. Coevolution of prostate cancer and bone stroma in three-dimensional coculture: implications for cancer growth and metastasis. Cancer Res. 2008;68(23):9996–10003.PubMedPubMedCentralCrossRef
8.
go back to reference Pittenger MF, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–7.PubMedCrossRef Pittenger MF, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–7.PubMedCrossRef
9.
go back to reference Dominici M, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7.PubMedCrossRef Dominici M, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7.PubMedCrossRef
10.
go back to reference Wakitani S, Saito T, Caplan AI. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve. 1995;18(12):1417–26.PubMedCrossRef Wakitani S, Saito T, Caplan AI. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve. 1995;18(12):1417–26.PubMedCrossRef
11.
go back to reference Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A. 1999;96(19):10711–6.PubMedPubMedCentralCrossRef Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A. 1999;96(19):10711–6.PubMedPubMedCentralCrossRef
13.
go back to reference Huang JI, et al. Rat extramedullary adipose tissue as a source of osteochondrogenic progenitor cells. Plast Reconstr Surg. 2002;109(3):1033–41. discussion 1042–3.PubMedCrossRef Huang JI, et al. Rat extramedullary adipose tissue as a source of osteochondrogenic progenitor cells. Plast Reconstr Surg. 2002;109(3):1033–41. discussion 1042–3.PubMedCrossRef
14.
go back to reference Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970;3(4):393–403.PubMed Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970;3(4):393–403.PubMed
15.
go back to reference Chamberlain G, et al. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007;25(11):2739–49.PubMedCrossRef Chamberlain G, et al. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007;25(11):2739–49.PubMedCrossRef
16.
go back to reference Ortiz LA, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A. 2003;100(14):8407–11.PubMedPubMedCentralCrossRef Ortiz LA, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A. 2003;100(14):8407–11.PubMedPubMedCentralCrossRef
17.
go back to reference Sato Y, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood. 2005;106(2):756–63.PubMedCrossRef Sato Y, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood. 2005;106(2):756–63.PubMedCrossRef
18.
go back to reference Ji JF, et al. Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells. 2004;22(3):415–27.PubMedCrossRef Ji JF, et al. Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells. 2004;22(3):415–27.PubMedCrossRef
19.
go back to reference Wu GD, et al. Migration of mesenchymal stem cells to heart allografts during chronic rejection. Transplantation. 2003;75(5):679–85.PubMedCrossRef Wu GD, et al. Migration of mesenchymal stem cells to heart allografts during chronic rejection. Transplantation. 2003;75(5):679–85.PubMedCrossRef
20.
go back to reference Serbina NV, Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol. 2006;7(3):311–7.PubMedCrossRef Serbina NV, Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol. 2006;7(3):311–7.PubMedCrossRef
21.
go back to reference Chitteti BR, et al. Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function. Blood. 2010;115(16):3239–48.PubMedPubMedCentralCrossRef Chitteti BR, et al. Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function. Blood. 2010;115(16):3239–48.PubMedPubMedCentralCrossRef
22.
go back to reference Almeida-Porada G, et al. Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation. Blood. 2000;95(11):3620–7.PubMed Almeida-Porada G, et al. Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation. Blood. 2000;95(11):3620–7.PubMed
23.
go back to reference Maitra B, et al. Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant. 2004;33(6):597–604.PubMedCrossRef Maitra B, et al. Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant. 2004;33(6):597–604.PubMedCrossRef
24.
go back to reference Ame-Thomas P, et al. Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis. Blood. 2007;109(2):693–702.PubMedCrossRef Ame-Thomas P, et al. Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis. Blood. 2007;109(2):693–702.PubMedCrossRef
25.
go back to reference Kansy BA, et al. The bidirectional tumor--mesenchymal stromal cell interaction promotes the progression of head and neck cancer. Stem Cell Res Ther. 2014;5(4):95.PubMedPubMedCentralCrossRef Kansy BA, et al. The bidirectional tumor--mesenchymal stromal cell interaction promotes the progression of head and neck cancer. Stem Cell Res Ther. 2014;5(4):95.PubMedPubMedCentralCrossRef
26.
go back to reference Karnoub AE, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449(7162):557–63.PubMedCrossRef Karnoub AE, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449(7162):557–63.PubMedCrossRef
28.
go back to reference Suzuki K, et al. Mesenchymal stromal cells promote tumor growth through the enhancement of neovascularization. Mol Med. 2011;17(7–8):579–87.PubMedPubMedCentral Suzuki K, et al. Mesenchymal stromal cells promote tumor growth through the enhancement of neovascularization. Mol Med. 2011;17(7–8):579–87.PubMedPubMedCentral
30.
go back to reference Brennen WN, et al. Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer. Oncotarget. 2013;4(1):106–17.PubMed Brennen WN, et al. Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer. Oncotarget. 2013;4(1):106–17.PubMed
31.
go back to reference Nabha SM, et al. Bone marrow stromal cells enhance prostate cancer cell invasion through type I collagen in an MMP-12 dependent manner. Int J Cancer. 2008;122(11):2482–90.PubMedCrossRef Nabha SM, et al. Bone marrow stromal cells enhance prostate cancer cell invasion through type I collagen in an MMP-12 dependent manner. Int J Cancer. 2008;122(11):2482–90.PubMedCrossRef
34.
go back to reference Hossain A, et al. Mesenchymal stem cells isolated from human gliomas increase proliferation and maintain stemness of glioma stem cells through the IL-6/gp130/STAT3 pathway. Stem Cells. 2015;33(8):2400–15.PubMedPubMedCentralCrossRef Hossain A, et al. Mesenchymal stem cells isolated from human gliomas increase proliferation and maintain stemness of glioma stem cells through the IL-6/gp130/STAT3 pathway. Stem Cells. 2015;33(8):2400–15.PubMedPubMedCentralCrossRef
35.
go back to reference Li W, et al. Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8. J Exp Clin Cancer Res. 2015;34:52.PubMedPubMedCentralCrossRef Li W, et al. Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8. J Exp Clin Cancer Res. 2015;34:52.PubMedPubMedCentralCrossRef
36.
go back to reference Zhu W, et al. Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol. 2006;80(3):267–74.PubMedCrossRef Zhu W, et al. Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol. 2006;80(3):267–74.PubMedCrossRef
37.
go back to reference Lacerda L, et al. Mesenchymal stem cells mediate the clinical phenotype of inflammatory breast cancer in a preclinical model. Breast Cancer Res. 2015;17:42.PubMedPubMedCentralCrossRef Lacerda L, et al. Mesenchymal stem cells mediate the clinical phenotype of inflammatory breast cancer in a preclinical model. Breast Cancer Res. 2015;17:42.PubMedPubMedCentralCrossRef
38.
go back to reference Ye H, et al. Human bone marrow-derived mesenchymal stem cells produced TGFbeta contributes to progression and metastasis of prostate cancer. Cancer Invest. 2012;30(7):513–8.PubMedCrossRef Ye H, et al. Human bone marrow-derived mesenchymal stem cells produced TGFbeta contributes to progression and metastasis of prostate cancer. Cancer Invest. 2012;30(7):513–8.PubMedCrossRef
39.
go back to reference Lee MJ, et al. Oncostatin M promotes mesenchymal stem cell-stimulated tumor growth through a paracrine mechanism involving periostin and TGFBI. Int J Biochem Cell Biol. 2013;45(8):1869–77.PubMedCrossRef Lee MJ, et al. Oncostatin M promotes mesenchymal stem cell-stimulated tumor growth through a paracrine mechanism involving periostin and TGFBI. Int J Biochem Cell Biol. 2013;45(8):1869–77.PubMedCrossRef
40.
go back to reference Costanza, B., et al. Stromal Modulators of TGF-beta in Cancer. J Clin Med. 2017. 6(1). Costanza, B., et al. Stromal Modulators of TGF-beta in Cancer. J Clin Med. 2017. 6(1).
41.
go back to reference Calon A, et al. Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for metastasis initiation. Cancer Cell. 2012;22(5):571–84.PubMedPubMedCentralCrossRef Calon A, et al. Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for metastasis initiation. Cancer Cell. 2012;22(5):571–84.PubMedPubMedCentralCrossRef
42.
go back to reference Richardsen E, et al. Immunohistochemical expression of epithelial and stromal immunomodulatory signalling molecules is a prognostic indicator in breast cancer. BMC Res Notes. 2012;5:110.PubMedPubMedCentralCrossRef Richardsen E, et al. Immunohistochemical expression of epithelial and stromal immunomodulatory signalling molecules is a prognostic indicator in breast cancer. BMC Res Notes. 2012;5:110.PubMedPubMedCentralCrossRef
43.
go back to reference Kim EK, et al. Endogenous gastric-resident mesenchymal stem cells contribute to formation of cancer stroma and progression of gastric cancer. Korean J Pathol. 2013;47(6):507–18.PubMedPubMedCentralCrossRef Kim EK, et al. Endogenous gastric-resident mesenchymal stem cells contribute to formation of cancer stroma and progression of gastric cancer. Korean J Pathol. 2013;47(6):507–18.PubMedPubMedCentralCrossRef
44.
go back to reference Sun B, et al. Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy. 2009;11(3):289–98. 1 p following 298.PubMedCrossRef Sun B, et al. Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy. 2009;11(3):289–98. 1 p following 298.PubMedCrossRef
45.
go back to reference Khakoo AY, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med. 2006;203(5):1235–47.PubMedPubMedCentralCrossRef Khakoo AY, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med. 2006;203(5):1235–47.PubMedPubMedCentralCrossRef
46.
go back to reference Qiao L, et al. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res. 2008;18(4):500–7.PubMedCrossRef Qiao L, et al. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res. 2008;18(4):500–7.PubMedCrossRef
48.
go back to reference Lee RH, et al. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol Biochem. 2004;14(4–6):311–24.PubMedCrossRef Lee RH, et al. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol Biochem. 2004;14(4–6):311–24.PubMedCrossRef
49.
go back to reference Wagner W, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol. 2005;33(11):1402–16.PubMedCrossRef Wagner W, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol. 2005;33(11):1402–16.PubMedCrossRef
50.
go back to reference Horwitz EM, et al. Clarification of the nomenclature for MSC: the international society for cellular therapy position statement. Cytotherapy. 2005;7(5):393–5.PubMedCrossRef Horwitz EM, et al. Clarification of the nomenclature for MSC: the international society for cellular therapy position statement. Cytotherapy. 2005;7(5):393–5.PubMedCrossRef
51.
go back to reference Riekstina U, et al. Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis. Stem Cell Rev. 2009;5(4):378–86.PubMedCrossRef Riekstina U, et al. Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis. Stem Cell Rev. 2009;5(4):378–86.PubMedCrossRef
52.
go back to reference Mantovani A, et al. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–55.PubMedCrossRef Mantovani A, et al. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–55.PubMedCrossRef
53.
go back to reference Sica A, Saccani A, Mantovani A. Tumor-associated macrophages: a molecular perspective. Int Immunopharmacol. 2002;2(8):1045–54.PubMedCrossRef Sica A, Saccani A, Mantovani A. Tumor-associated macrophages: a molecular perspective. Int Immunopharmacol. 2002;2(8):1045–54.PubMedCrossRef
54.
go back to reference Allavena P, et al. The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev. 2008;222:155–61.PubMedCrossRef Allavena P, et al. The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev. 2008;222:155–61.PubMedCrossRef
55.
go back to reference Sica A, et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006;42(6):717–27.PubMedCrossRef Sica A, et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006;42(6):717–27.PubMedCrossRef
56.
go back to reference Solinas G, et al. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol. 2009;86(5):1065–73.PubMedCrossRef Solinas G, et al. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol. 2009;86(5):1065–73.PubMedCrossRef
57.
go back to reference Tomchuck SL, et al. Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells. 2008;26(1):99–107.PubMedCrossRef Tomchuck SL, et al. Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells. 2008;26(1):99–107.PubMedCrossRef
58.
go back to reference Waterman RS, et al. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One. 2010;5(4):e10088.PubMedPubMedCentralCrossRef Waterman RS, et al. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One. 2010;5(4):e10088.PubMedPubMedCentralCrossRef
59.
go back to reference Waterman RS, Henkle SL, Betancourt AM. Mesenchymal stem cell 1 (MSC1)-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis. PLoS One. 2012;7(9):e45590.PubMedPubMedCentralCrossRef Waterman RS, Henkle SL, Betancourt AM. Mesenchymal stem cell 1 (MSC1)-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis. PLoS One. 2012;7(9):e45590.PubMedPubMedCentralCrossRef
61.
go back to reference Spaeth EL, et al. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS One. 2009;4(4):e4992.PubMedPubMedCentralCrossRef Spaeth EL, et al. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS One. 2009;4(4):e4992.PubMedPubMedCentralCrossRef
62.
go back to reference Evans RA, et al. TGF-beta1-mediated fibroblast-myofibroblast terminal differentiation-the role of Smad proteins. Exp Cell Res. 2003;282(2):90–100.PubMedCrossRef Evans RA, et al. TGF-beta1-mediated fibroblast-myofibroblast terminal differentiation-the role of Smad proteins. Exp Cell Res. 2003;282(2):90–100.PubMedCrossRef
63.
go back to reference Zeisberg EM, et al. Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts. Cancer Res. 2007;67(21):10123–8.PubMedCrossRef Zeisberg EM, et al. Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts. Cancer Res. 2007;67(21):10123–8.PubMedCrossRef
64.
go back to reference Kojima Y, et al. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A. 2010;107(46):20009–14.PubMedPubMedCentralCrossRef Kojima Y, et al. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A. 2010;107(46):20009–14.PubMedPubMedCentralCrossRef
65.
go back to reference Shangguan L, et al. Inhibition of TGF-beta/Smad signaling by BAMBI blocks differentiation of human mesenchymal stem cells to carcinoma-associated fibroblasts and abolishes their protumor effects. Stem Cells. 2012;30(12):2810–9.PubMedCrossRef Shangguan L, et al. Inhibition of TGF-beta/Smad signaling by BAMBI blocks differentiation of human mesenchymal stem cells to carcinoma-associated fibroblasts and abolishes their protumor effects. Stem Cells. 2012;30(12):2810–9.PubMedCrossRef
66.
go back to reference Calon A, Tauriello DV, Batlle E. TGF-beta in CAF-mediated tumor growth and metastasis. Semin Cancer Biol. 2014;25:15–22.PubMedCrossRef Calon A, Tauriello DV, Batlle E. TGF-beta in CAF-mediated tumor growth and metastasis. Semin Cancer Biol. 2014;25:15–22.PubMedCrossRef
67.
go back to reference Direkze NC, et al. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res. 2004;64(23):8492–5.PubMedCrossRef Direkze NC, et al. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res. 2004;64(23):8492–5.PubMedCrossRef
68.
go back to reference Ishii G, et al. Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction. Biochem Biophys Res Commun. 2003;309(1):232–40.PubMedCrossRef Ishii G, et al. Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction. Biochem Biophys Res Commun. 2003;309(1):232–40.PubMedCrossRef
69.
go back to reference Direkze NC, et al. Bone marrow-derived stromal cells express lineage-related messenger RNA species. Cancer Res. 2006;66(3):1265–9.PubMedCrossRef Direkze NC, et al. Bone marrow-derived stromal cells express lineage-related messenger RNA species. Cancer Res. 2006;66(3):1265–9.PubMedCrossRef
71.
go back to reference Peng Y, Li Z, Li Z. GRP78 secreted by tumor cells stimulates differentiation of bone marrow mesenchymal stem cells to cancer-associated fibroblasts. Biochem Biophys Res Commun. 2013;440(4):558–63.PubMedCrossRef Peng Y, Li Z, Li Z. GRP78 secreted by tumor cells stimulates differentiation of bone marrow mesenchymal stem cells to cancer-associated fibroblasts. Biochem Biophys Res Commun. 2013;440(4):558–63.PubMedCrossRef
72.
go back to reference Paunescu V, et al. Tumour-associated fibroblasts and mesenchymal stem cells: more similarities than differences. J Cell Mol Med. 2011;15(3):635–46.PubMedCrossRef Paunescu V, et al. Tumour-associated fibroblasts and mesenchymal stem cells: more similarities than differences. J Cell Mol Med. 2011;15(3):635–46.PubMedCrossRef
73.
75.
go back to reference Albarenque SM, Zwacka RM, Mohr A. Both human and mouse mesenchymal stem cells promote breast cancer metastasis. Stem Cell Res. 2011;7(2):163–71.PubMedCrossRef Albarenque SM, Zwacka RM, Mohr A. Both human and mouse mesenchymal stem cells promote breast cancer metastasis. Stem Cell Res. 2011;7(2):163–71.PubMedCrossRef
76.
go back to reference Shinagawa K, et al. Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer. 2010;127(10):2323–33.PubMedCrossRef Shinagawa K, et al. Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer. 2010;127(10):2323–33.PubMedCrossRef
77.
go back to reference Chaturvedi P, et al. Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. J Clin Invest. 2013;123(1):189–205.PubMed Chaturvedi P, et al. Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. J Clin Invest. 2013;123(1):189–205.PubMed
78.
go back to reference Loebinger MR, et al. Magnetic resonance imaging of mesenchymal stem cells homing to pulmonary metastases using biocompatible magnetic nanoparticles. Cancer Res. 2009;69(23):8862–7.PubMedPubMedCentralCrossRef Loebinger MR, et al. Magnetic resonance imaging of mesenchymal stem cells homing to pulmonary metastases using biocompatible magnetic nanoparticles. Cancer Res. 2009;69(23):8862–7.PubMedPubMedCentralCrossRef
79.
80.
go back to reference Martin FT, et al. Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Res Treat. 2010;124(2):317–26.PubMedCrossRef Martin FT, et al. Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Res Treat. 2010;124(2):317–26.PubMedCrossRef
81.
go back to reference Xue Z, et al. Mesenchymal stem cells promote epithelial to mesenchymal transition and metastasis in gastric cancer though paracrine cues and close physical contact. J Cell Biochem. 2015;116(4):618–27.PubMedCrossRef Xue Z, et al. Mesenchymal stem cells promote epithelial to mesenchymal transition and metastasis in gastric cancer though paracrine cues and close physical contact. J Cell Biochem. 2015;116(4):618–27.PubMedCrossRef
82.
go back to reference Jing Y, et al. Mesenchymal stem cells in inflammation microenvironment accelerates hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition. PLoS One. 2012;7(8):e43272.PubMedPubMedCentralCrossRef Jing Y, et al. Mesenchymal stem cells in inflammation microenvironment accelerates hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition. PLoS One. 2012;7(8):e43272.PubMedPubMedCentralCrossRef
83.
go back to reference Xu WT, et al. Human mesenchymal stem cells (hMSCs) target osteosarcoma and promote its growth and pulmonary metastasis. Cancer Lett. 2009;281(1):32–41.PubMedCrossRef Xu WT, et al. Human mesenchymal stem cells (hMSCs) target osteosarcoma and promote its growth and pulmonary metastasis. Cancer Lett. 2009;281(1):32–41.PubMedCrossRef
85.
go back to reference Hu DD, et al. A biochemical characterization of the binding of osteopontin to integrins alpha v beta 1 and alpha v beta 5. J Biol Chem. 1995;270(44):26232–8.PubMedCrossRef Hu DD, et al. A biochemical characterization of the binding of osteopontin to integrins alpha v beta 1 and alpha v beta 5. J Biol Chem. 1995;270(44):26232–8.PubMedCrossRef
86.
go back to reference Liaw L, et al. The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro. J Clin Invest. 1995;95(2):713–24.PubMedPubMedCentralCrossRef Liaw L, et al. The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro. J Clin Invest. 1995;95(2):713–24.PubMedPubMedCentralCrossRef
87.
go back to reference Denda S, Reichardt LF, Muller U. Identification of osteopontin as a novel ligand for the integrin alpha8 beta1 and potential roles for this integrin-ligand interaction in kidney morphogenesis. Mol Biol Cell. 1998;9(6):1425–35.PubMedPubMedCentralCrossRef Denda S, Reichardt LF, Muller U. Identification of osteopontin as a novel ligand for the integrin alpha8 beta1 and potential roles for this integrin-ligand interaction in kidney morphogenesis. Mol Biol Cell. 1998;9(6):1425–35.PubMedPubMedCentralCrossRef
88.
go back to reference Yokosaki Y, et al. The integrin alpha(9)beta(1) binds to a novel recognition sequence (SVVYGLR) in the thrombin-cleaved amino-terminal fragment of osteopontin. J Biol Chem. 1999;274(51):36328–34.PubMedCrossRef Yokosaki Y, et al. The integrin alpha(9)beta(1) binds to a novel recognition sequence (SVVYGLR) in the thrombin-cleaved amino-terminal fragment of osteopontin. J Biol Chem. 1999;274(51):36328–34.PubMedCrossRef
89.
go back to reference Khodavirdi AC, et al. Increased expression of osteopontin contributes to the progression of prostate cancer. Cancer Res. 2006;66(2):883–8.PubMedCrossRef Khodavirdi AC, et al. Increased expression of osteopontin contributes to the progression of prostate cancer. Cancer Res. 2006;66(2):883–8.PubMedCrossRef
90.
go back to reference Castellano G, et al. Activation of the osteopontin/matrix metalloproteinase-9 pathway correlates with prostate cancer progression. Clin Cancer Res. 2008;14(22):7470–80.PubMedCrossRef Castellano G, et al. Activation of the osteopontin/matrix metalloproteinase-9 pathway correlates with prostate cancer progression. Clin Cancer Res. 2008;14(22):7470–80.PubMedCrossRef
91.
go back to reference Forootan SS, et al. Prognostic significance of osteopontin expression in human prostate cancer. Int J Cancer. 2006;118(9):2255–61.PubMedCrossRef Forootan SS, et al. Prognostic significance of osteopontin expression in human prostate cancer. Int J Cancer. 2006;118(9):2255–61.PubMedCrossRef
92.
go back to reference Ramankulov A, et al. Plasma osteopontin in comparison with bone markers as indicator of bone metastasis and survival outcome in patients with prostate cancer. Prostate. 2007;67(3):330–40.PubMedCrossRef Ramankulov A, et al. Plasma osteopontin in comparison with bone markers as indicator of bone metastasis and survival outcome in patients with prostate cancer. Prostate. 2007;67(3):330–40.PubMedCrossRef
93.
go back to reference Nemoto H, et al. Osteopontin deficiency reduces experimental tumor cell metastasis to bone and soft tissues. J Bone Miner Res. 2001;16(4):652–9.PubMedCrossRef Nemoto H, et al. Osteopontin deficiency reduces experimental tumor cell metastasis to bone and soft tissues. J Bone Miner Res. 2001;16(4):652–9.PubMedCrossRef
94.
go back to reference Ishijima M, et al. Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin. J Exp Med. 2001;193(3):399–404.PubMedPubMedCentralCrossRef Ishijima M, et al. Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin. J Exp Med. 2001;193(3):399–404.PubMedPubMedCentralCrossRef
95.
go back to reference Chellaiah MA, et al. Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression. Mol Biol Cell. 2003;14(1):173–89.PubMedPubMedCentralCrossRef Chellaiah MA, et al. Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression. Mol Biol Cell. 2003;14(1):173–89.PubMedPubMedCentralCrossRef
97.
go back to reference Ross FP, et al. Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption. J Biol Chem. 1993;268(13):9901–7.PubMed Ross FP, et al. Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption. J Biol Chem. 1993;268(13):9901–7.PubMed
98.
go back to reference Yamate T, et al. Osteopontin expression by osteoclast and osteoblast progenitors in the murine bone marrow: demonstration of its requirement for osteoclastogenesis and its increase after ovariectomy. Endocrinology. 1997;138(7):3047–55.PubMed Yamate T, et al. Osteopontin expression by osteoclast and osteoblast progenitors in the murine bone marrow: demonstration of its requirement for osteoclastogenesis and its increase after ovariectomy. Endocrinology. 1997;138(7):3047–55.PubMed
99.
go back to reference Ibrahim T, et al. Expression of bone sialoprotein and osteopontin in breast cancer bone metastases. Clin Exp Metastasis. 2000;18(3):253–60.PubMedCrossRef Ibrahim T, et al. Expression of bone sialoprotein and osteopontin in breast cancer bone metastases. Clin Exp Metastasis. 2000;18(3):253–60.PubMedCrossRef
100.
go back to reference Adwan H, Bauerle TJ, Berger MR. Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells. Cancer Gene Ther. 2004;11(2):109–20.PubMedCrossRef Adwan H, Bauerle TJ, Berger MR. Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells. Cancer Gene Ther. 2004;11(2):109–20.PubMedCrossRef
101.
102.
go back to reference Cooper CR, et al. Stromal factors involved in prostate carcinoma metastasis to bone. Cancer. 2003;97(3 Suppl):739–47.PubMedCrossRef Cooper CR, et al. Stromal factors involved in prostate carcinoma metastasis to bone. Cancer. 2003;97(3 Suppl):739–47.PubMedCrossRef
104.
go back to reference Taichman RS, et al. Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res. 2002;62(6):1832–7.PubMed Taichman RS, et al. Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res. 2002;62(6):1832–7.PubMed
105.
go back to reference Singh S, et al. CXCL12-CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion. Lab Invest. 2004;84(12):1666–76.PubMedCrossRef Singh S, et al. CXCL12-CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion. Lab Invest. 2004;84(12):1666–76.PubMedCrossRef
106.
107.
go back to reference Nishimori, H., et al. Prostate cancer cells and bone stromal cells mutually interact with each other through bone morphogenetic protein-mediated signals. J Biol Chem. 2012;287(24):20037-46. Nishimori, H., et al. Prostate cancer cells and bone stromal cells mutually interact with each other through bone morphogenetic protein-mediated signals. J Biol Chem. 2012;287(24):20037-46.
108.
go back to reference Joseph J, et al. Disseminated prostate cancer cells can instruct hematopoietic stem and progenitor cells to regulate bone phenotype. Mol Cancer Res. 2012;10(3):282–92.PubMedPubMedCentralCrossRef Joseph J, et al. Disseminated prostate cancer cells can instruct hematopoietic stem and progenitor cells to regulate bone phenotype. Mol Cancer Res. 2012;10(3):282–92.PubMedPubMedCentralCrossRef
109.
go back to reference Hodge DR, Hurt EM, Farrar WL. The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer. 2005;41(16):2502–12.PubMedCrossRef Hodge DR, Hurt EM, Farrar WL. The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer. 2005;41(16):2502–12.PubMedCrossRef
110.
go back to reference Thomas X, et al. Interdependence between cytokines and cell adhesion molecules to induce interleukin-6 production by stromal cells in myeloma. Leuk Lymphoma. 1998;32(1–2):107–19.PubMedCrossRef Thomas X, et al. Interdependence between cytokines and cell adhesion molecules to induce interleukin-6 production by stromal cells in myeloma. Leuk Lymphoma. 1998;32(1–2):107–19.PubMedCrossRef
111.
go back to reference Michigami T, et al. Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and alpha(4)beta(1)-integrin enhances production of osteoclast-stimulating activity. Blood. 2000;96(5):1953–60.PubMed Michigami T, et al. Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and alpha(4)beta(1)-integrin enhances production of osteoclast-stimulating activity. Blood. 2000;96(5):1953–60.PubMed
112.
go back to reference Ara T, et al. Interleukin-6 in the bone marrow microenvironment promotes the growth and survival of neuroblastoma cells. Cancer Res. 2009;69(1):329–37.PubMedPubMedCentralCrossRef Ara T, et al. Interleukin-6 in the bone marrow microenvironment promotes the growth and survival of neuroblastoma cells. Cancer Res. 2009;69(1):329–37.PubMedPubMedCentralCrossRef
113.
go back to reference Brocke-Heidrich K, et al. Interleukin-6-dependent gene expression profiles in multiple myeloma INA-6 cells reveal a Bcl-2 family-independent survival pathway closely associated with Stat3 activation. Blood. 2004;103(1):242–51.PubMedCrossRef Brocke-Heidrich K, et al. Interleukin-6-dependent gene expression profiles in multiple myeloma INA-6 cells reveal a Bcl-2 family-independent survival pathway closely associated with Stat3 activation. Blood. 2004;103(1):242–51.PubMedCrossRef
114.
go back to reference Klopp AH, et al. Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells. 2011;29(1):11–9.PubMedCrossRef Klopp AH, et al. Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells. 2011;29(1):11–9.PubMedCrossRef
115.
go back to reference Farmer P, et al. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med. 2009;15(1):68–74.PubMedCrossRef Farmer P, et al. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med. 2009;15(1):68–74.PubMedCrossRef
116.
go back to reference Finak G, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008;14(5):518–27.PubMedCrossRef Finak G, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008;14(5):518–27.PubMedCrossRef
117.
go back to reference Skolekova S, et al. Cisplatin-induced mesenchymal stromal cells-mediated mechanism contributing to decreased antitumor effect in breast cancer cells. Cell Commun Signal. 2016;14(1):4.PubMedPubMedCentralCrossRef Skolekova S, et al. Cisplatin-induced mesenchymal stromal cells-mediated mechanism contributing to decreased antitumor effect in breast cancer cells. Cell Commun Signal. 2016;14(1):4.PubMedPubMedCentralCrossRef
Metadata
Title
Mesenchymal stem cells: key players in cancer progression
Authors
Sarah M. Ridge
Francis J. Sullivan
Sharon A. Glynn
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0597-8

Other articles of this Issue 1/2017

Molecular Cancer 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine