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Published in: Indian Journal of Surgery 3/2013

01-06-2013 | Review Article

Breast Cancer Stem Cells, Pathways and Therapeutic Perspectives 2011

Author: Anjana Nigam

Published in: Indian Journal of Surgery | Issue 3/2013

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Abstract

The evidence for the existence of a heterogeneous population of cancer stem cells (CSCs) responsible for the initiation and maintenance of cancer has been characterized for several tumors recently. Purification and molecular characterization of normal human mammary stem cells from cultured mammospheres has been achieved, providing evidence supporting a model in which breast tumor heterogeneity is a reflection of a number of CSC-like cells in the tumor. A number of experimental methodologies have been developed to characterize epithelial stem cells, including the expression of cell surface or intracellular markers, mammosphere formation, exclusion of fluorescent dye by a side population, retention of the radionucleotide label, etc. Methodologies have also been successfully employed to identify tumorigenic cells within breast cancers. The most important characteristics of stem cells are the capacity for self-renewal and the regulation of the balance between self-renewal and differentiation. In the mammary gland, signaling pathways, such as Hedgehog (Hh), Wnt/β-catenin, and Notch, play a role in embryogenesis and organogenesis and maintenance of tissues in the adult through regulation of the balance between self-renewal and differentiation of stem cells. Breast TAAs include epitopes from proteins, such as carcinoembryonic antigen and NYBR-1, which are involved in tissue differentiation. Targeting BCSCs may be achieved by a number of approaches such as chemotherapy sensitization of BCSCs, differentiating therapy, targeting stem cell elimination, targeting signaling pathways and drug transporters, and inhibition of regulatory pathways involved in self-renewal. Targeting cells which have the potential to metastasize will be an important aspect of the BCSC field as these are the cells that cause the majority of morbidity and mortality from breast cancer.
Literature
1.
go back to reference Kakarala M, Wicha MS (2008) Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol 10(26):2813–2820 Kakarala M, Wicha MS (2008) Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol 10(26):2813–2820
2.
go back to reference Wong JF (2007) Probing the biology of cancer stem cells: AACR sheds light on the microenvironment to better target these cells and their pathways. Genet Eng Biotech News 27(10) Wong JF (2007) Probing the biology of cancer stem cells: AACR sheds light on the microenvironment to better target these cells and their pathways. Genet Eng Biotech News 27(10)
3.
go back to reference Korkaya H, Paulson A, Iovino F, Wicha MS (2008) HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 27:6120–6130PubMedCentralPubMed Korkaya H, Paulson A, Iovino F, Wicha MS (2008) HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 27:6120–6130PubMedCentralPubMed
4.
go back to reference Chiou SH, Yu CC, Huang CY, Lin SC, Liu CJ, Tsai TH, Chou SH, Chien CS, Ku HH, Lo JF (2008) Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and highgrade oral squamous cell carcinoma. Clin Cancer Res 14:4085–4095PubMed Chiou SH, Yu CC, Huang CY, Lin SC, Liu CJ, Tsai TH, Chou SH, Chien CS, Ku HH, Lo JF (2008) Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and highgrade oral squamous cell carcinoma. Clin Cancer Res 14:4085–4095PubMed
5.
go back to reference Okamoto OK, Perez JF (2008) Targeting cancer stem cells with monoclonal antibodies: a new perspective in cancer therapy and diagnosis. Expert Rev MolDiagn 8:387–393 Okamoto OK, Perez JF (2008) Targeting cancer stem cells with monoclonal antibodies: a new perspective in cancer therapy and diagnosis. Expert Rev MolDiagn 8:387–393
6.
go back to reference Stiles CD, Rowitch DH (2008) Glioma stem cells: a midterm exam. Neuron 58:832–846PubMed Stiles CD, Rowitch DH (2008) Glioma stem cells: a midterm exam. Neuron 58:832–846PubMed
7.
go back to reference Annabi B, Rojas-Sutterlin S, Laflamme C, Lachambre MP, Rolland Y, Sartelet H, Beliveau R (2008) Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. Mol Cancer Res 6:907–916PubMed Annabi B, Rojas-Sutterlin S, Laflamme C, Lachambre MP, Rolland Y, Sartelet H, Beliveau R (2008) Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. Mol Cancer Res 6:907–916PubMed
8.
go back to reference Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737PubMed Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737PubMed
9.
go back to reference Singh S, Hawkins C, Clarke I, Squire J, Bayani J, Hide T, Henkelman R, Cusimano M, Dirks P (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401PubMed Singh S, Hawkins C, Clarke I, Squire J, Bayani J, Hide T, Henkelman R, Cusimano M, Dirks P (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401PubMed
10.
go back to reference Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65:5506–5511PubMed Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65:5506–5511PubMed
11.
go back to reference Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988PubMedCentralPubMed Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988PubMedCentralPubMed
12.
go back to reference Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, Bernard L, Viale G, Pelicci PG, Di Fiore PP (2010) Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 140(1):62–73PubMed Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, Bernard L, Viale G, Pelicci PG, Di Fiore PP (2010) Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 140(1):62–73PubMed
13.
go back to reference Soeda A, Park M, Lee D et al (2009) Hypoxia promotes expansion of the CD133− positive glioma stem cells through activation of HIF-1α. Oncogene 28(45):3949–3959PubMed Soeda A, Park M, Lee D et al (2009) Hypoxia promotes expansion of the CD133− positive glioma stem cells through activation of HIF-1α. Oncogene 28(45):3949–3959PubMed
14.
go back to reference Chen R, Nishimura MC, Bumbaca SM, Kharbanda S, Forrest WF, Kasman IM, Greve JM, Soriano RH, Gilmour LL, Rivers CS, Modrusan Z, Nacu S, Guerrero S, Edgar KA, Wallin JJ, Lamszus K, Westphal M, Heim S, James CD, Vanden Berg SR, Costello JF, Moorefield S, Cowdrey CJ, Prados M, Phillips HS (2010) A hierarchy of self-renewing tumor-initiating cell types in glioblastoma. Cancer Cell 17:362–375PubMed Chen R, Nishimura MC, Bumbaca SM, Kharbanda S, Forrest WF, Kasman IM, Greve JM, Soriano RH, Gilmour LL, Rivers CS, Modrusan Z, Nacu S, Guerrero S, Edgar KA, Wallin JJ, Lamszus K, Westphal M, Heim S, James CD, Vanden Berg SR, Costello JF, Moorefield S, Cowdrey CJ, Prados M, Phillips HS (2010) A hierarchy of self-renewing tumor-initiating cell types in glioblastoma. Cancer Cell 17:362–375PubMed
15.
go back to reference Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194:23–28PubMed Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194:23–28PubMed
16.
go back to reference Liang Y, Zhong Z, Huang Y, Deng W, Cao J, Tsao G, Liu Q, Pei D, Kang T, Zeng YX (2010) Stem-like cancer cells are inducible by increasing genomic instability in cancer cell. J Biol Chem 285(7):4931–4940PubMedCentralPubMed Liang Y, Zhong Z, Huang Y, Deng W, Cao J, Tsao G, Liu Q, Pei D, Kang T, Zeng YX (2010) Stem-like cancer cells are inducible by increasing genomic instability in cancer cell. J Biol Chem 285(7):4931–4940PubMedCentralPubMed
18.
go back to reference Li Y, Welm B, Podsypanina K, Huang S, Chamorro M, Zhang X, Rowlands T, Egeblad M, Cowin P, Werb Z et al (2003) Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci USA 100:15853–15858PubMedCentralPubMed Li Y, Welm B, Podsypanina K, Huang S, Chamorro M, Zhang X, Rowlands T, Egeblad M, Cowin P, Werb Z et al (2003) Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci USA 100:15853–15858PubMedCentralPubMed
19.
go back to reference Lynch MD, Cariati M, Purushotham AD (2006) Breast cancer, stem cells and prospects for therapy. Breast Cancer Res 8:211PubMedCentralPubMed Lynch MD, Cariati M, Purushotham AD (2006) Breast cancer, stem cells and prospects for therapy. Breast Cancer Res 8:211PubMedCentralPubMed
20.
go back to reference Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE (2006) Generation of a functional mammary gland from a single stem cell. Nature 439:84–88PubMed Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE (2006) Generation of a functional mammary gland from a single stem cell. Nature 439:84–88PubMed
21.
go back to reference Simic P, Vukicevic S (2005) Bone morphogenetic proteins in development and homeostasis of kidney. Cytokine Growth Factor Rev 16:299–308PubMed Simic P, Vukicevic S (2005) Bone morphogenetic proteins in development and homeostasis of kidney. Cytokine Growth Factor Rev 16:299–308PubMed
22.
go back to reference Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454PubMed Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454PubMed
23.
go back to reference Yingling JM, Blanchard KL, Sawyer JS (2004) Development of TGF-β signalling inhibitors for cancer therapy. Nat Rev Drug Discov 3:1011–1022PubMed Yingling JM, Blanchard KL, Sawyer JS (2004) Development of TGF-β signalling inhibitors for cancer therapy. Nat Rev Drug Discov 3:1011–1022PubMed
24.
go back to reference Deckers M, van Dinther M, Buijs J, Que I, Lowik C, van der Pluijm G, ten Dijke P (2006) The tumor suppressor Smad4 is required for transforming growth factor β-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Res 66:2202–2209PubMed Deckers M, van Dinther M, Buijs J, Que I, Lowik C, van der Pluijm G, ten Dijke P (2006) The tumor suppressor Smad4 is required for transforming growth factor β-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Res 66:2202–2209PubMed
25.
go back to reference Buijs JT, Henriquez NV, van Overveld PG, van der Horst G, Que I, Schwaninger R, Rentsch C, Ten Dijke P, Cleton-Jansen AM, Driouch K, Lidereau R, Bachelier R, Vukicevic S, Clézardin P, Papapoulos SE, Cecchini MG, Löwik CW, van der Pluijm G (2007) Bone morphogenetic protein 7 in the development and treatment of bone metastasesfrom breast cancer. Cancer Res 67(18):8742–8751PubMed Buijs JT, Henriquez NV, van Overveld PG, van der Horst G, Que I, Schwaninger R, Rentsch C, Ten Dijke P, Cleton-Jansen AM, Driouch K, Lidereau R, Bachelier R, Vukicevic S, Clézardin P, Papapoulos SE, Cecchini MG, Löwik CW, van der Pluijm G (2007) Bone morphogenetic protein 7 in the development and treatment of bone metastasesfrom breast cancer. Cancer Res 67(18):8742–8751PubMed
26.
go back to reference Schwalbe M, Sanger J, Eggers R, Naumann A, Schmidt A, Hoffken K, Clement JH (2003) Differential expression and regulation of bone morphogenetic protein 7 in breast cancer. Int J Oncol 23:89–95PubMed Schwalbe M, Sanger J, Eggers R, Naumann A, Schmidt A, Hoffken K, Clement JH (2003) Differential expression and regulation of bone morphogenetic protein 7 in breast cancer. Int J Oncol 23:89–95PubMed
27.
go back to reference Takahashi M, Otsuka F, Miyoshi T, Otani H, Goto J, Yamashita M, Ogura T, Makino H, Doihara H (2008) Bone morphogenetic protein 6 (BMP6) and BMP7 inhibit estrogen-induced proliferation of breast cancer cells by suppressing p38 mitogen-activated protein kinase activation. J Endocrinol 199(3):445–455PubMed Takahashi M, Otsuka F, Miyoshi T, Otani H, Goto J, Yamashita M, Ogura T, Makino H, Doihara H (2008) Bone morphogenetic protein 6 (BMP6) and BMP7 inhibit estrogen-induced proliferation of breast cancer cells by suppressing p38 mitogen-activated protein kinase activation. J Endocrinol 199(3):445–455PubMed
28.
go back to reference Wong DJ, Liu H, Ridky TW, Cassarino D, Segal E, Chang HY (2008) Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2:333–344PubMedCentralPubMed Wong DJ, Liu H, Ridky TW, Cassarino D, Segal E, Chang HY (2008) Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2:333–344PubMedCentralPubMed
29.
go back to reference Honeth G, Bendahl PO, Ringner M, Saal LH, Gruvberger-Saal SK, Lovgren K, Grabau D, Ferno M, Borg A, Hegardt C (2008) CD44+/CD24-phenotype is enriched in basallike breast tumors. Breast Cancer Res 10:R53PubMedCentralPubMed Honeth G, Bendahl PO, Ringner M, Saal LH, Gruvberger-Saal SK, Lovgren K, Grabau D, Ferno M, Borg A, Hegardt C (2008) CD44+/CD24-phenotype is enriched in basallike breast tumors. Breast Cancer Res 10:R53PubMedCentralPubMed
30.
go back to reference Morrison BJ, Schmidt CW, Sunil R, Lakhani SR, Brent A, Reynolds BA, Lopez JA (2008) Breast cancer stem cells: implications for therapy of breast cancer. Breast Cancer Res 10:210PubMedCentralPubMed Morrison BJ, Schmidt CW, Sunil R, Lakhani SR, Brent A, Reynolds BA, Lopez JA (2008) Breast cancer stem cells: implications for therapy of breast cancer. Breast Cancer Res 10:210PubMedCentralPubMed
31.
go back to reference Savagner P (2010) The epithelial-mesenchymal transition (EMT) phenomenon. Ann Oncol 21(Suppl 7):vii89–vii92PubMed Savagner P (2010) The epithelial-mesenchymal transition (EMT) phenomenon. Ann Oncol 21(Suppl 7):vii89–vii92PubMed
32.
go back to reference Savagner P (2001) Leaving the neighborhood: molecular mechanisms involved during epithelial-mesenchymal transition. Bioessays 23:912–923PubMed Savagner P (2001) Leaving the neighborhood: molecular mechanisms involved during epithelial-mesenchymal transition. Bioessays 23:912–923PubMed
33.
go back to reference Thiery J (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890PubMed Thiery J (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890PubMed
34.
go back to reference Berx G, Raspe E, Christofori G, Thiery JP, Sleeman JP (2007) Pre-EMTing metastasis? Recapitulation of morphogenetic processes in cancer. Clin Exp Metastasis 24:587–597PubMed Berx G, Raspe E, Christofori G, Thiery JP, Sleeman JP (2007) Pre-EMTing metastasis? Recapitulation of morphogenetic processes in cancer. Clin Exp Metastasis 24:587–597PubMed
35.
go back to reference Arnoux V, Come C, Kusewitt DF, Hudson L, Savagner P (2005) Cutaneous wound healing: a partial and reversible EMT. In: Savagner P (ed) Rise and Fall of Epithelial Phenotype: Concepts of Epithelial–Mesenchyme Transition. Springer, Berlin, pp 111–134 Arnoux V, Come C, Kusewitt DF, Hudson L, Savagner P (2005) Cutaneous wound healing: a partial and reversible EMT. In: Savagner P (ed) Rise and Fall of Epithelial Phenotype: Concepts of Epithelial–Mesenchyme Transition. Springer, Berlin, pp 111–134
36.
go back to reference Morel A, Lievre M, Thomas C, Hinkal G, Ansieau S, Puisieux A (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 3:e2888PubMedCentralPubMed Morel A, Lievre M, Thomas C, Hinkal G, Ansieau S, Puisieux A (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 3:e2888PubMedCentralPubMed
37.
go back to reference Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715PubMedCentralPubMed Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715PubMedCentralPubMed
38.
go back to reference Wyatt L, Wadham C, Crocker LA, Lardelli M, Khew-Goodall Y (2007) The protein tyrosine phosphatase Pez regulates TGFbeta, epithelial-mesenchymal transition, and organ development. J Cell Biol 178:1223–1235PubMedCentralPubMed Wyatt L, Wadham C, Crocker LA, Lardelli M, Khew-Goodall Y (2007) The protein tyrosine phosphatase Pez regulates TGFbeta, epithelial-mesenchymal transition, and organ development. J Cell Biol 178:1223–1235PubMedCentralPubMed
39.
go back to reference Waerner T, Alacakaptan M, Tamir I, Oberauer R, Gal A, Brabletz T, Schreiber M, Jechlinger M, Beug H (2006) ILEI: a cytokine essential for EMT, tumor formation, and late events in metastasis in epithelial cells. Cancer Cell 10:227–239PubMed Waerner T, Alacakaptan M, Tamir I, Oberauer R, Gal A, Brabletz T, Schreiber M, Jechlinger M, Beug H (2006) ILEI: a cytokine essential for EMT, tumor formation, and late events in metastasis in epithelial cells. Cancer Cell 10:227–239PubMed
40.
go back to reference Beach S, Tang H, Park S, Dhillon AS, Keller ET, Kolch W, Yeung KC (2008) Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene 27:2243–2248PubMedCentralPubMed Beach S, Tang H, Park S, Dhillon AS, Keller ET, Kolch W, Yeung KC (2008) Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene 27:2243–2248PubMedCentralPubMed
41.
go back to reference Zhuang Z, Lininger RA, Man YG, Albuquerque A, Merino MJ, Tavassoli FA (1997) Identical clonality of both components of mammary carcinosarcoma with differential loss of heterozygosity. Mod Pathol 10:354–362PubMed Zhuang Z, Lininger RA, Man YG, Albuquerque A, Merino MJ, Tavassoli FA (1997) Identical clonality of both components of mammary carcinosarcoma with differential loss of heterozygosity. Mod Pathol 10:354–362PubMed
42.
go back to reference Saegusa M, Hashimura M, Kuwata T, Okayasu I (2009) Requirement of the Akt/beta-catenin pathway for uterine carcinosarcoma genesis, modulating E-cadherin expression through the transactivation of slug. Am J Pathol 174:2107–2115PubMedCentralPubMed Saegusa M, Hashimura M, Kuwata T, Okayasu I (2009) Requirement of the Akt/beta-catenin pathway for uterine carcinosarcoma genesis, modulating E-cadherin expression through the transactivation of slug. Am J Pathol 174:2107–2115PubMedCentralPubMed
43.
go back to reference Berx G, Cleton-Jansen AM, Strumane K, de Leeuw WJ, Nollet F, van Roy F, Cornelisse C (1996) E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene 13:1919–1925PubMed Berx G, Cleton-Jansen AM, Strumane K, de Leeuw WJ, Nollet F, van Roy F, Cornelisse C (1996) E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene 13:1919–1925PubMed
44.
go back to reference Moll R, Mitze M, Frixen UH, Birchmeier W (1993) Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol 143:1731–1742PubMedCentralPubMed Moll R, Mitze M, Frixen UH, Birchmeier W (1993) Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol 143:1731–1742PubMedCentralPubMed
45.
go back to reference Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927–939PubMed Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927–939PubMed
46.
go back to reference Patel SA, Heinrich AC, Reddy BY, Srinivas B, Heidaran N, Rameshwar P (2008) Breast cancer biology: the multifaceted roles of mesenchymal stem cells. J Oncol 2008:425895PubMedCentralPubMed Patel SA, Heinrich AC, Reddy BY, Srinivas B, Heidaran N, Rameshwar P (2008) Breast cancer biology: the multifaceted roles of mesenchymal stem cells. J Oncol 2008:425895PubMedCentralPubMed
47.
go back to reference Greco SJ, Rameshwar P (2007) MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. Proc Natl Acad Sci USA 104(39):15484–15489PubMedCentralPubMed Greco SJ, Rameshwar P (2007) MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. Proc Natl Acad Sci USA 104(39):15484–15489PubMedCentralPubMed
48.
go back to reference Metz RL, Patel PS, Hameed M, Bryan M, Rameshwar P (2007) Role of human HGFIN/nmb in breast cancer. Breast Cancer Res 9:1–10 Metz RL, Patel PS, Hameed M, Bryan M, Rameshwar P (2007) Role of human HGFIN/nmb in breast cancer. Breast Cancer Res 9:1–10
49.
go back to reference Corcoran KE, Rameshwar P (2007) Nuclear factor-κB accounts for the repressor effects of high stromal cell-derived factor-1α levels on Tac1 expression in nontumorigenic breast cells. Mol Cancer Res 5:373–381PubMed Corcoran KE, Rameshwar P (2007) Nuclear factor-κB accounts for the repressor effects of high stromal cell-derived factor-1α levels on Tac1 expression in nontumorigenic breast cells. Mol Cancer Res 5:373–381PubMed
50.
go back to reference Pantel K, Brakenhoff RH (2004) Dissecting the metastatic cascade. Nat Rev Cancer 4:448–456PubMed Pantel K, Brakenhoff RH (2004) Dissecting the metastatic cascade. Nat Rev Cancer 4:448–456PubMed
51.
go back to reference Cristofanilli M, Hayes D, Budd G, Ellis M, Stopeck A, Reuben J, Doyle G, Matera J, Allard W, Miller M, Fritsche HA, Hortobagyi GN, Terstappen LW (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420–1430PubMed Cristofanilli M, Hayes D, Budd G, Ellis M, Stopeck A, Reuben J, Doyle G, Matera J, Allard W, Miller M, Fritsche HA, Hortobagyi GN, Terstappen LW (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420–1430PubMed
52.
go back to reference Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verástegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50–56PubMed Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verástegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50–56PubMed
53.
go back to reference Pang R, Law WL, Chu AC, Poon JT, Lam CS, Chow AK, Ng L, Cheung LW, Lan XR, Lan HY, Tan VP, Yau TC, Poon RT, Wong BC (2010) A subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell 6(6):603–615PubMed Pang R, Law WL, Chu AC, Poon JT, Lam CS, Chow AK, Ng L, Cheung LW, Lan XR, Lan HY, Tan VP, Yau TC, Poon RT, Wong BC (2010) A subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell 6(6):603–615PubMed
54.
go back to reference Vaillant F, Asselin-Labat ML, Shackleton M, Lindeman GJ, Visvader JE (2007) The emerging picture of the mouse mammary stem cell. Stem Cell Rev 3:114–123PubMed Vaillant F, Asselin-Labat ML, Shackleton M, Lindeman GJ, Visvader JE (2007) The emerging picture of the mouse mammary stem cell. Stem Cell Rev 3:114–123PubMed
55.
go back to reference Liu S, Ginestier C, Charafe-Jauffret E, Foco H, Kleer CG, Merajver SD, Dontu G, Wicha MS (2008) BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci USA 105:1680–1685PubMedCentralPubMed Liu S, Ginestier C, Charafe-Jauffret E, Foco H, Kleer CG, Merajver SD, Dontu G, Wicha MS (2008) BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci USA 105:1680–1685PubMedCentralPubMed
56.
go back to reference Narod SA, Foulkes WD (2004) BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 4:665–676PubMed Narod SA, Foulkes WD (2004) BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 4:665–676PubMed
57.
go back to reference Dontu G, El-Ashry D, Wicha MS (2004) Breast cancer, stem/progenitor cells and the estrogen receptor. Trends Endocrinol Metab 15:193–197PubMed Dontu G, El-Ashry D, Wicha MS (2004) Breast cancer, stem/progenitor cells and the estrogen receptor. Trends Endocrinol Metab 15:193–197PubMed
58.
go back to reference Gaiano N, Fishell G (2002) The role of Notch in promoting glial and neural stem cell fates. Ann Rev Neurosci 25:471–490PubMed Gaiano N, Fishell G (2002) The role of Notch in promoting glial and neural stem cell fates. Ann Rev Neurosci 25:471–490PubMed
59.
go back to reference Uyttendaele H, Soriano JV, Montesano R, Kitajewski J (1998) Notch4 and Wnt-1 proteins function to regulate branching morphogenesis of mammary epithelial cells in an opposing fashion. Dev Biol 196:204–217PubMed Uyttendaele H, Soriano JV, Montesano R, Kitajewski J (1998) Notch4 and Wnt-1 proteins function to regulate branching morphogenesis of mammary epithelial cells in an opposing fashion. Dev Biol 196:204–217PubMed
60.
go back to reference Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17:1253–1270PubMedCentralPubMed Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17:1253–1270PubMedCentralPubMed
61.
go back to reference Tepera SB, McCrea PD, Rosen JM (2003) A beta-catenin survival signal is required for normal lobular development in the mammary gland. J Cell Sci 116:1137–1149PubMed Tepera SB, McCrea PD, Rosen JM (2003) A beta-catenin survival signal is required for normal lobular development in the mammary gland. J Cell Sci 116:1137–1149PubMed
62.
go back to reference Schroeder JA, Adriance MC, McConnell EJ, Thompson MC, Pockaj B, Gendler SJ (2002) ErbB-beta-catenin complexes are associated with human infiltrating ductal breast and murine mammary tumor virus (MMTV)-Wnt-1 and MMTV-c-Neu transgenic carcinomas. J Biol Chem 277:22692–22698PubMed Schroeder JA, Adriance MC, McConnell EJ, Thompson MC, Pockaj B, Gendler SJ (2002) ErbB-beta-catenin complexes are associated with human infiltrating ductal breast and murine mammary tumor virus (MMTV)-Wnt-1 and MMTV-c-Neu transgenic carcinomas. J Biol Chem 277:22692–22698PubMed
63.
go back to reference Hahn H, Wicking C, Zaphiropoulos PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE (1996) Mutations of the human homolog of drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85:841–851PubMed Hahn H, Wicking C, Zaphiropoulos PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE (1996) Mutations of the human homolog of drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85:841–851PubMed
64.
go back to reference Kubo M, Nakamura M, Tasaki A, Yamanaka N, Nakashima H, Nomura M, Kuroki S, Katano M (2004) Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res 64:6071–6074PubMed Kubo M, Nakamura M, Tasaki A, Yamanaka N, Nakashima H, Nomura M, Kuroki S, Katano M (2004) Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res 64:6071–6074PubMed
65.
go back to reference Lewis MT, Ross S, Strickland PA, Sugnet CW, Jimenez E, Scott MP, Daniel CW (1999) Defects in mouse mammary gland development caused by conditional haploinsufficiency of Patched-1. Development 126:5181–5193PubMed Lewis MT, Ross S, Strickland PA, Sugnet CW, Jimenez E, Scott MP, Daniel CW (1999) Defects in mouse mammary gland development caused by conditional haploinsufficiency of Patched-1. Development 126:5181–5193PubMed
66.
go back to reference Hui C, Daniel CW (2001) The Gli2 transcription factor is required for normal mouse mammary gland development. Dev Biol 238:133–144PubMed Hui C, Daniel CW (2001) The Gli2 transcription factor is required for normal mouse mammary gland development. Dev Biol 238:133–144PubMed
67.
go back to reference Theurillat JP, Zurrer-Hardi U, Varga Z, Storz M, Probst-Hensch NM, Seifert B, Fehr MK, Fink D, Ferrone S, Pestalozzi B, Jungbluth AA, Chen YT, Jäger D, Knuth A, Moch H (2007) NY-BR-1 protein expression in breast carcinoma: a mammary gland differentiation antigen as target for cancer immunotherapy. Cancer Immunol Immunother 56:1723–1731PubMed Theurillat JP, Zurrer-Hardi U, Varga Z, Storz M, Probst-Hensch NM, Seifert B, Fehr MK, Fink D, Ferrone S, Pestalozzi B, Jungbluth AA, Chen YT, Jäger D, Knuth A, Moch H (2007) NY-BR-1 protein expression in breast carcinoma: a mammary gland differentiation antigen as target for cancer immunotherapy. Cancer Immunol Immunother 56:1723–1731PubMed
68.
go back to reference Pinzon-Charry A, Schmidt C, Lopez JA (2006) Dendritic cell immunotherapy for breast cancer. Expert Opin Biol Ther 6:591–604PubMed Pinzon-Charry A, Schmidt C, Lopez JA (2006) Dendritic cell immunotherapy for breast cancer. Expert Opin Biol Ther 6:591–604PubMed
69.
go back to reference Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lønning P, Børresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874PubMedCentralPubMed Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lønning P, Børresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874PubMedCentralPubMed
70.
go back to reference Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 Is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567PubMedCentralPubMed Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 Is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567PubMedCentralPubMed
71.
go back to reference Miletti-Gonzalez KE, Chen S, Muthukumaran N, Saglimbeni GN, Wu X, Yang J, Apolito K, Shih WJ, Hait WN, Rodriguez-Rodriguez L (2005) The CD44 receptor interacts with P-glycoprotein to promote cell migration and invasion in cancer. Cancer Res 65:6660–6667PubMed Miletti-Gonzalez KE, Chen S, Muthukumaran N, Saglimbeni GN, Wu X, Yang J, Apolito K, Shih WJ, Hait WN, Rodriguez-Rodriguez L (2005) The CD44 receptor interacts with P-glycoprotein to promote cell migration and invasion in cancer. Cancer Res 65:6660–6667PubMed
72.
go back to reference Engelmann K, Shen H, Finn OJ (2008) MCF7 side population cells with characteristics of cancer stem/progenitor cells express the tumor antigen MUC1. Cancer Res 68:2419–2426PubMed Engelmann K, Shen H, Finn OJ (2008) MCF7 side population cells with characteristics of cancer stem/progenitor cells express the tumor antigen MUC1. Cancer Res 68:2419–2426PubMed
73.
go back to reference Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV, Varticovski L (2008) Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res 10:R10PubMedCentralPubMed Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV, Varticovski L (2008) Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res 10:R10PubMedCentralPubMed
74.
go back to reference Phillips T, McBride W, Pajonk F (2006) The response of CD24(-/low)/CD44+ breast cancer initiating cells to radiation. J Natl Cancer Inst 98:1777–1785PubMed Phillips T, McBride W, Pajonk F (2006) The response of CD24(-/low)/CD44+ breast cancer initiating cells to radiation. J Natl Cancer Inst 98:1777–1785PubMed
75.
go back to reference Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5:275–284PubMed Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5:275–284PubMed
76.
go back to reference Norgaard JM, Olesen LH, Hokland P (2004) Changing picture of cellular drug resistance in human leukemia. Crit Rev Oncol Hematol 50:39–49PubMed Norgaard JM, Olesen LH, Hokland P (2004) Changing picture of cellular drug resistance in human leukemia. Crit Rev Oncol Hematol 50:39–49PubMed
77.
go back to reference Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD (1998) A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 95:15665–15670PubMedCentralPubMed Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD (1998) A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 95:15665–15670PubMedCentralPubMed
78.
go back to reference Thomas H, Coley HM (2003) Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glyco-protein. Cancer Control 10:159–165PubMed Thomas H, Coley HM (2003) Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glyco-protein. Cancer Control 10:159–165PubMed
79.
go back to reference Massard C, Deutsch E, Soria JC (2006) Tumour stem cell-targeted treatment: elimination or differentiation. Ann Oncol 17:1620–1624PubMed Massard C, Deutsch E, Soria JC (2006) Tumour stem cell-targeted treatment: elimination or differentiation. Ann Oncol 17:1620–1624PubMed
80.
go back to reference Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138(4):645–659PubMed Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138(4):645–659PubMed
81.
go back to reference Eddy SF, Kane SE, Sonenshein GE (2007) Trastuzumab-resistant HER2-driven breast cancer cells are sensitive to epigallocate-chin-3 gallate. Cancer Res 67:9018–9023PubMed Eddy SF, Kane SE, Sonenshein GE (2007) Trastuzumab-resistant HER2-driven breast cancer cells are sensitive to epigallocate-chin-3 gallate. Cancer Res 67:9018–9023PubMed
82.
go back to reference Ting AH, McGarvey KM, Baylin SB (2006) The cancer epigenome—components andfunctional correlates. Genes Dev 20:3215–3231PubMed Ting AH, McGarvey KM, Baylin SB (2006) The cancer epigenome—components andfunctional correlates. Genes Dev 20:3215–3231PubMed
83.
go back to reference Gunther EJ, Moody SE, Belka GK, Hahn KT, Innocent N, Dugan KD, Cardiff RD, Chodosh LA (2003) Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis. Genes Dev 17:488–501PubMedCentralPubMed Gunther EJ, Moody SE, Belka GK, Hahn KT, Innocent N, Dugan KD, Cardiff RD, Chodosh LA (2003) Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis. Genes Dev 17:488–501PubMedCentralPubMed
84.
go back to reference Luu HH, Zhang R, Haydon RC, Rayburn E, Kang Q, Si W, Park JK, Wang H, Peng Y, Jiang W, He TC (2004) Wnt/beta-catenin signaling pathway as a novel cancer drug target. Curr Cancer Drug Targets 4:653–671PubMed Luu HH, Zhang R, Haydon RC, Rayburn E, Kang Q, Si W, Park JK, Wang H, Peng Y, Jiang W, He TC (2004) Wnt/beta-catenin signaling pathway as a novel cancer drug target. Curr Cancer Drug Targets 4:653–671PubMed
85.
go back to reference Zhou L, An N, Haydon RC, Zhou Q, Cheng H, Peng Y, Jiang W, Luu HH, Vanichakarn P, Szatkowski JP, Park JY, Breyer B, He TC (2003) Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the beta-catenin signaling activity. Cancer Lett 193:161–170PubMed Zhou L, An N, Haydon RC, Zhou Q, Cheng H, Peng Y, Jiang W, Luu HH, Vanichakarn P, Szatkowski JP, Park JY, Breyer B, He TC (2003) Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the beta-catenin signaling activity. Cancer Lett 193:161–170PubMed
86.
go back to reference Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM, Wicha MS (2004) Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res 6:R605–R615PubMedCentralPubMed Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM, Wicha MS (2004) Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res 6:R605–R615PubMedCentralPubMed
87.
go back to reference Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, Wong H, Rosen J, Chang JC (2008) Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 100:672–679PubMed Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, Wong H, Rosen J, Chang JC (2008) Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 100:672–679PubMed
88.
go back to reference Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, Guan JL, Dontu G, Wicha MS (2010) CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest 120(2):485–497PubMedCentralPubMed Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, Guan JL, Dontu G, Wicha MS (2010) CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest 120(2):485–497PubMedCentralPubMed
89.
go back to reference Banchereau J, Steinman R (1998) Dendritic cells and the control of immunity. Nature 392:245–252PubMed Banchereau J, Steinman R (1998) Dendritic cells and the control of immunity. Nature 392:245–252PubMed
90.
go back to reference Hollenbeak CS, Todd MM, Billingsley EM, Harper G, Dyer AM, Lengerich EJ (2005) Increased incidence of melanoma in renal transplantation recipients. Cancer 104:1962–1967PubMed Hollenbeak CS, Todd MM, Billingsley EM, Harper G, Dyer AM, Lengerich EJ (2005) Increased incidence of melanoma in renal transplantation recipients. Cancer 104:1962–1967PubMed
91.
go back to reference Menard S, Tomasic G, Casalini P, Balsari A, Pilotti S, Cascinelli N, Salvadori B, Colnaghi MI, Rilke F (1997) Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas. Clin Cancer Res 3:817–819PubMed Menard S, Tomasic G, Casalini P, Balsari A, Pilotti S, Cascinelli N, Salvadori B, Colnaghi MI, Rilke F (1997) Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas. Clin Cancer Res 3:817–819PubMed
92.
go back to reference Gabrilovich DI, Corak J, Ciernik IF, Kavanaugh D, Carbone DP (1997) Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res 3:483–490PubMed Gabrilovich DI, Corak J, Ciernik IF, Kavanaugh D, Carbone DP (1997) Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res 3:483–490PubMed
93.
go back to reference Della Bella S, Gennaro M, Vaccari M, Ferraris C, Nicola S, Riva A, Clerici M, Greco M, Villa ML (2003) Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer 89:1463–1472PubMedCentralPubMed Della Bella S, Gennaro M, Vaccari M, Ferraris C, Nicola S, Riva A, Clerici M, Greco M, Villa ML (2003) Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer 89:1463–1472PubMedCentralPubMed
94.
go back to reference Pinzon-Charry A, Maxwell T, McGuckin MA, Schmidt CW, Furnival C, Lopez JA (2006) Spontaneous apoptosis of blood dendritic cells in patients with breast cancer. Breast Cancer Res 8:R5PubMedCentralPubMed Pinzon-Charry A, Maxwell T, McGuckin MA, Schmidt CW, Furnival C, Lopez JA (2006) Spontaneous apoptosis of blood dendritic cells in patients with breast cancer. Breast Cancer Res 8:R5PubMedCentralPubMed
95.
go back to reference Mocellin S, Mandruzzato S, Bronte V, Lise M, Nitti D (2004) Part I: Vaccines for solid tumours. Lancet Oncol 5:681–689PubMed Mocellin S, Mandruzzato S, Bronte V, Lise M, Nitti D (2004) Part I: Vaccines for solid tumours. Lancet Oncol 5:681–689PubMed
96.
go back to reference Sakai Y, Morrison BJ, Burke JD, Park JM, Terabe M, Janik JE, Forni G, Berzofsky JA, Morris JC (2004) Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice. Cancer Res 64:8022–8028PubMed Sakai Y, Morrison BJ, Burke JD, Park JM, Terabe M, Janik JE, Forni G, Berzofsky JA, Morris JC (2004) Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice. Cancer Res 64:8022–8028PubMed
97.
go back to reference Ridgway D (2003) The first 1000 dendritic cell vaccinees. Cancer Invest 21:873–886PubMed Ridgway D (2003) The first 1000 dendritic cell vaccinees. Cancer Invest 21:873–886PubMed
98.
go back to reference Panelli MC, Wunderlich J, Jeffries J, Wang E, Mixon A, Rosenberg SA, Marincola FM (2000) Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. J Immunother 23:487–498PubMed Panelli MC, Wunderlich J, Jeffries J, Wang E, Mixon A, Rosenberg SA, Marincola FM (2000) Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. J Immunother 23:487–498PubMed
99.
go back to reference Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, Pineiro L, Steinman R, Fay J (2001) Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res 61:6451–6458PubMed Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, Pineiro L, Steinman R, Fay J (2001) Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res 61:6451–6458PubMed
100.
go back to reference Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W (2000) Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptidepulsed dendritic cells. Blood 96:3102–3108PubMed Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W (2000) Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptidepulsed dendritic cells. Blood 96:3102–3108PubMed
101.
go back to reference Wrzesinski C, Paulos CM, Gattinoni L, Palmer DC, Kaiser A, Yu Z, Rosenberg SA, Restifo NP (2007) Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8+ T cells. J Clin Invest 117:492–501PubMedCentralPubMed Wrzesinski C, Paulos CM, Gattinoni L, Palmer DC, Kaiser A, Yu Z, Rosenberg SA, Restifo NP (2007) Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8+ T cells. J Clin Invest 117:492–501PubMedCentralPubMed
102.
go back to reference Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA (2002) Stemness: transcriptional profiling of embryonic and adult stem cells. Science 298:597–600PubMed Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA (2002) Stemness: transcriptional profiling of embryonic and adult stem cells. Science 298:597–600PubMed
103.
go back to reference Li Y, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, Yu Y, Clouthier SG, Schwartz SJ, Wicha MS, Sun D (2010) Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res 16(9):2580–2590PubMedCentralPubMed Li Y, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, Yu Y, Clouthier SG, Schwartz SJ, Wicha MS, Sun D (2010) Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res 16(9):2580–2590PubMedCentralPubMed
105.
go back to reference Taborga M, Corcoran KE, Fernandes N, Ramkissoon SH, Rameshwar P (2007) Gcoupled protein receptors and breast cancer progression: potential drug targets. Mini Rev Med Chem 7(3):245–251PubMed Taborga M, Corcoran KE, Fernandes N, Ramkissoon SH, Rameshwar P (2007) Gcoupled protein receptors and breast cancer progression: potential drug targets. Mini Rev Med Chem 7(3):245–251PubMed
106.
go back to reference Bandari PS, Qian J, Yehia G, Joshi DD, Maloof PB, Potian J, Oh HS, Gascon P, Harrison JS, Rameshwar P (2003) Hematopoietic growth factor inducible neurokinin-1 type: a transmembrane protein that is similar to neurokinin 1 interacts with substance P. Regul Pept 111(1–3):169–178PubMed Bandari PS, Qian J, Yehia G, Joshi DD, Maloof PB, Potian J, Oh HS, Gascon P, Harrison JS, Rameshwar P (2003) Hematopoietic growth factor inducible neurokinin-1 type: a transmembrane protein that is similar to neurokinin 1 interacts with substance P. Regul Pept 111(1–3):169–178PubMed
107.
go back to reference Rameshwar P (2007) Implication of possible therapies targeted for the tachykinergic system with the biology of neurokinin receptors and emerging related proteins. Recent Pat CNS Drug Discov 2(1):79–84PubMed Rameshwar P (2007) Implication of possible therapies targeted for the tachykinergic system with the biology of neurokinin receptors and emerging related proteins. Recent Pat CNS Drug Discov 2(1):79–84PubMed
108.
go back to reference Kretzschmar M (2000) Transforming growth factor-β and breast cancer: transforming growth factor-β/SMAD signaling defects and cancer. Breast Cancer Res 2:107–115PubMedCentralPubMed Kretzschmar M (2000) Transforming growth factor-β and breast cancer: transforming growth factor-β/SMAD signaling defects and cancer. Breast Cancer Res 2:107–115PubMedCentralPubMed
109.
go back to reference Yang J, Song K, Krebs TL, Jackson MW, Danielpour D (2008) Rb/E2F4 and Smad2/3 link survivin to TGF-β-induced apoptosis and tumor progression. Oncogene 27:5326–5338PubMedCentralPubMed Yang J, Song K, Krebs TL, Jackson MW, Danielpour D (2008) Rb/E2F4 and Smad2/3 link survivin to TGF-β-induced apoptosis and tumor progression. Oncogene 27:5326–5338PubMedCentralPubMed
110.
go back to reference Oh HS, Moharita A, Potian JG, Whitehead IP, Livingston JC, Castro TA, Patel PS, Rameshwar P (2004) Bone marrow stroma influences transforming growth factor-β production in breast cancer cells to regulate c-myc activation of the preprotachykinin-I gene in breast cancer cells. Cancer Res 64:6327–6336PubMed Oh HS, Moharita A, Potian JG, Whitehead IP, Livingston JC, Castro TA, Patel PS, Rameshwar P (2004) Bone marrow stroma influences transforming growth factor-β production in breast cancer cells to regulate c-myc activation of the preprotachykinin-I gene in breast cancer cells. Cancer Res 64:6327–6336PubMed
111.
go back to reference Parmiani G, Russo V, Marrari A, Cutolo G, Casati C, Pilla L, Maccalli C, Rivoltini L, Castelli C (2007) Universal and stemness-related tumor antigens: potential use in cancer immunotherapy. Clin Cancer Res 13:5675–5679PubMed Parmiani G, Russo V, Marrari A, Cutolo G, Casati C, Pilla L, Maccalli C, Rivoltini L, Castelli C (2007) Universal and stemness-related tumor antigens: potential use in cancer immunotherapy. Clin Cancer Res 13:5675–5679PubMed
112.
go back to reference Lou H, Dean M (2007) Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 26:1357–1360PubMed Lou H, Dean M (2007) Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 26:1357–1360PubMed
113.
go back to reference Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel MA (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101:14228–14233PubMedCentralPubMed Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel MA (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101:14228–14233PubMedCentralPubMed
Metadata
Title
Breast Cancer Stem Cells, Pathways and Therapeutic Perspectives 2011
Author
Anjana Nigam
Publication date
01-06-2013
Publisher
Springer India
Published in
Indian Journal of Surgery / Issue 3/2013
Print ISSN: 0972-2068
Electronic ISSN: 0973-9793
DOI
https://doi.org/10.1007/s12262-012-0616-3

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