Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Breast Cancer Stem Cells and Sex Steroid Hormones

Author(s): Iván Flores-Ramírez, Noemi Baranda-Avila* and Elizabeth Langley

Volume 14, Issue 5, 2019

Page: [398 - 404] Pages: 7

DOI: 10.2174/1574888X13666180810121415

Price: $65

conference banner
Abstract

Breast cancer stem cells (BCSCs) are a small population of tumor-initiating cells that express stem cell-associated markers. In recent years, their properties and mechanisms of regulation have become the focus of intense research due to their intrinsic resistance to conventional cancer therapies. This review describes breast cancer stem cell origin, signaling pathways involved in self-renewal, such as Wnt, Notch and Hedgehog, biomarkers linked to stemness, and the role of sex steroid hormones in BCSC regulation.

Keywords: Breast cancer, breast cancer stem cells, biomarkers, signaling pathways, estrogen receptor, progesterone receptor.

[1]
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87-108.
[2]
Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v10, Cancer Incidence and Mortality Worldwide: IARC CancerBase No 11. Lyon, France: International Agency for Research on Cancer 2013. http://globocan.iarc.fr (Accessed on February 21, 2018).
[3]
Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med 1998; 339(22): 1609-18.
[4]
Filipova A, Seifrtova M, Mokry J, et al. Breast cancer and cancer stem cells: A mini-review. Tumori 2014; 100(4): 363-9.
[5]
Velasco-Velázquez MA, Homsi N, De La Fuente M, Pestell RG. Breast cancer stem cells. Int J Biochem Cell Biol 2012; 44(4): 573-7.
[6]
Park EY, Chang E, Lee EJ, et al. Targeting of miR34a-NOTCH1 axis reduced breast cancer stemness and chemoresistance. Cancer Res 2014; 74(24): 7573-82.
[7]
Fan W, Chang J, Fu P. Endocrine therapy resistance in breast cancer: current status, possible mechanisms and overcoming strategies. Future Med Chem 2015; 7(12): 1511-9.
[8]
Wang JC, Dick JE. Cancer stem cells: Lessons from leukemia. Trends Cell Biol 2005; 15(9): 494-501.
[9]
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100(7): 3983-8.
[10]
Willis RE. Targeted cancer therapy: Vital oncogenes and a new molecular genetic paradigm for cancer initiation progression and treatment. Int J Mol Sci 2016; 17(9)E1552
[11]
Hwang-Verslues WW, Chang KJ, Lee EY, Lee WH. Breast cancer stem cells and tumor suppressor genes. J Formos Med Assoc 2008; 107(10): 751-66.
[12]
Bao L, Cardiff RD, Steinbach P, Messer KS, Ellies LG. Multipotent luminal mammary cancer stem cells model tumor heterogeneity. Breast Cancer Res 2015; 17(1): 137.
[13]
Krivtsov AV, Twomey D, Feng Z, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 2006; 442(7104): 818-22.
[14]
Liao Y. Cancer, stem cell misplacement and cancer stem cells. J Cell Mol Med 2013; 17(9): 1194-5.
[15]
Wang RA, Li ZS, Zhang HZ, et al. Invasive cancers are not necessarily from preformed in situ tumours - an alternative way of carcinogenesis from misplaced stem cells. J Cell Mol Med 2013; 17(7): 921-6.
[16]
May CD, Sphyris N, Evans KW, Werden SJ, Guo W, Mani SA. Epithelial-mesenchymal transition and cancer stem cells: a dangerously dynamic duo in breast cancer progression. Breast Cancer Res 2011; 13(1): 202.
[17]
Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133(4): 704-15.
[18]
Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 2006; 66(12): 6063-71.
[19]
Memmi EM, Sanarico AG, Giacobbe A, et al. p63 Sustains self-renewal of mammary cancer stem cells through regulation of Sonic Hedgehog signaling. Proc Natl Acad Sci USA 2015; 112(11): 3499-504.
[20]
Zhou W, Wang G, Guo S. Regulation of angiogenesis via Notch signaling in breast cancer and cancer stem cells. Biochim Biophys Acta 2013; 1836(2): 304-20.
[21]
D’Angelo RC, Ouzounova M, Davis A, et al. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity. Mol Cancer Ther 2015; 14(3): 779-87.
[22]
Grudzien P, Lo S, Albain KS, et al. Inhibition of Notch signaling reduces the stem-like population of breast cancer cells and prevents mammosphere formation. Anticancer Res 2010; 30(10): 3853-67.
[23]
Harrison H, Farnie G, Howell SJ, et al. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res 2010; 70(2): 709-18.
[24]
Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 1982; 31: 99-109.
[25]
Zeng YA, Nusse R. Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture. Cell Stem Cell 2010; 6(6): 568-77.
[26]
Kaufhold S, Garbán H, Bonavida B. Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication. J Exp Clin Cancer Res 2016; 35: 84.
[27]
Lee S, Wottrich S, Bonavida B. Crosstalks between Raf-kinase inhibitor protein and cancer stem cell transcription factors (Oct4, KLF4, Sox2, Nanog). Tumour Biol 2017; 39(4)1010428317692253
[28]
Ren H, Du P, Ge Z, et al. TWIST1 and BMI1 in cancer metastasis and chemoresistance. J Cancer 2016; 7(9): 1074-80.
[29]
Williams K, Motiani K, Giridhar PV, Kasper S. CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches. Exp Biol Med (Maywood) 2013; 238(3): 324-38.
[30]
Afify A, Purnell P, Nguyen L. Role of CD44s and CD44v6 on human breast cancer cell adhesion, migration, and invasion. Exp Mol Pathol 2009; 86(2): 95-100.
[31]
Olsson E, Honeth G, Bendahl PO, et al. CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers. BMC Cancer 2011; 11: 418.
[32]
Xu H, Tian Y, Yuan X, et al. Enrichment of CD44 in basal-type breast cancer correlates with EMT, cancer stem cell gene profile, and prognosis. OncoTargets Ther 2016; 9: 431-44.
[33]
Joensuu H, Klemi PJ, Toikkanen S, Jalkanen S. Glycoprotein CD44 expression and its association with survival in breast cancer. Am J Pathol 1993; 143(3): 867-74.
[34]
Friedrichs K, Franke F, Lisboa BW, et al. CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer. Cancer Res 1995; 55(22): 5424-33.
[35]
Diaz LK, Zhou X, Wright ET, et al. CD44 expression is associated with increased survival in node-negative invasive breast carcinoma. Clin Cancer Res 2005; 11(9): 3309-14.
[36]
Jaggupilli A, Elkord E. Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clin Dev Immunol 2012; 2012708036
[37]
Schabath H, Runz S, Joumaa S, Altevogt P. CD24 affects CXCR4 function in pre-B lymphocytes and breast carcinoma cells. J Cell Sci 2006; 119(Pt 2): 314-25.
[38]
Baumann P, Cremers N, Kroese F, et al. CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res 2005; 65(23): 10783-93.
[39]
Kim HJ, Kim MJ, Ahn SH, et al. Different prognostic significance of CD24 and CD44 expression in breast cancer according to hormone receptor status. Breast 2011; 20(1): 78-85.
[40]
Ricardo S, Vieira AF, Gerhard R, et al. Breast cancer stem cell markers CD44, CD24 and ALDH1: Expression distribution within intrinsic molecular subtype. J Clin Pathol 2011; 4(11): 937-46.
[41]
Shipitsin M, Campbell LL, Argani P, et al. Molecular definition of breast tumor heterogeneity. Cancer Cell 2007; 11(3): 259-73.
[42]
Bozorgi A, Khazaei M, Khazaei MR. New findings on breast cancer stem cells: A review. J Breast Cancer 2015; 18(4): 303-12.
[43]
Perrone G, Gaeta LM, Zagami M, et al. In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas. PLoS One 2012; 7(9)e43110
[44]
Wang LB, He YQ, Wu LG, Chen DM, Fan H, Jia W. Isolation and characterization of human breast tumor stem cells. Xibao Yu Fenzi Mianyixue Zazhi 2012; 28: 1261-4.
[45]
Sheridan C, Kishimoto H, Fuchs RK, et al. CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res 2006; 8(5): R59.
[46]
Leth-Larsen R, Terp MG, Christensen AG, et al. Functional heterogeneity within the CD44 high human breast cancer stem cell-like compartment reveals a gene signature predictive of distant metastasis. Mol Med 2012; 18: 1109-21.
[47]
Abraham BK, Fritz P, McClellan M, Hauptvogel P, Athelogou M, Brauch H. Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res 2005; 11(3): 1154-9.
[48]
Idowu MO, Kmieciak M, Dumur C, et al. CD44(+)/CD24(-/low) cancer stem/progenitor cells are more abundant in triple-negative invasive breast carcinoma phenotype and are associated with poor outcome. Hum Pathol 2012; 43(3): 364-73.
[49]
Vasiliou V, Nebert DW. Analysis and update of the human aldehyde dehydrogenase (ALDH) gene family. Hum Genomics 2005; 2(2): 138-43.
[50]
Sládek NE. Human aldehyde dehydrogenases: Potential pathological, pharmacological, and toxicological impact. J Biochem Mol Toxicol 2003; 17(1): 7-23.
[51]
Chute JP, Muramoto GG, Whitesides J, et al. Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc Natl Acad Sci USA 2006; 103(31): 11707-12.
[52]
Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007; 1(5): 555-67.
[53]
Morimoto K, Kim SJ, Tanei T, et al. Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression. Cancer Sci 2009; 100(6): 1062-8.
[54]
Park SY, Lee HE, Li H, Shipitsin M, Gelman R, Polyak K. Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res 2010; 16(3): 876-87.
[55]
Neumeister V, Rimm D. Is ALDH1 a good method for definition of breast cancer stem cells? Breast Cancer Res Treat 2010; 123(1): 109-11.
[56]
Marcato P, Dean CA, Pan D, et al. Aldehyde dehydrogenase activity of breast cancer stem cells is primarily due to isoform ALDH1A3 and its expression is predictive of metastasis. Stem Cells 2011; 29(1): 32-45.
[57]
Cariati M, Naderi A, Brown JP, et al. Alpha-6 integrin is necessary for the tumourigenicity of a stem cell like subpopulation within the MCF7 breast cancer cell line. Int J Cancer 2008; 122: 298-304.
[58]
Vaillant F, Asselin-Labat ML, Shackleton M, Forrest NC, Lindeman GJ, Visvader JE. The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res 2008; 68: 7711-7.
[59]
Meyer MJ, Fleming JM, Lin AF, Hussnain SA, Ginsburg E, Vonderhaar BK. CD44posCD49fhiCD133/2hi defines xenograft-initiating cells in estrogen receptor-negative breast cancer. Cancer Res 2010; 70: 4624-33.
[60]
Kim SJ, Kim YS, Jang ED, Seo KJ, Kim JS. Prognostic Impact and Clinicopathological Correlation of CD133 and ALDH1 Expression in Invasive Breast Cancer. J Breast Cancer 2015; 18: 347-55.
[61]
Grange C, Lanzardo S, Cavallo F, Camussi G, Bussolati B. Sca-1 identifies the tumor-initiating cells in mammary tumors of BALB-neuT transgenic mice. Neoplasia 2008; 10(12): 1433-43.
[62]
Ye F, Zhong X, Qiu Y, et al. CD49f can act as a biomarker for local or distant recurrence in breast cancer. J Breast Cancer 2017; 20(2): 142-9.
[63]
Ablett MP, O’Brien CS, Sims AH, Farnie G, Clarke RB. A differential role for CXCR4 in the regulation of normal versus malignant breast stem cell activity. Oncotarget 2014; 5(3): 599-612.
[64]
Krohn A, Song YH, Muehlberg F, Droll L, Beckmann C, Alt E. CXCR4 receptor positive spheroid forming cells are responsible for tumor invasion in vitro. Cancer Lett 2009; 280(1): 65-71.
[65]
Asiedu MK, Ingle JN, Behrens MD, Radisky DC, Knutson KL. TGFbeta/TNF(alpha)-mediated epithelial-mesenchymal transition generates breast cancer stem cells with a claudin-low phenotype. Cancer Res 2011; 71(13): 4707-19.
[66]
Trautmann F, Cojoc M, Kurth I, et al. CXCR4 as biomarker for radioresistant cancer stem cells. Int J Radiat Biol 2014; 90(8): 687-99.
[67]
Boyle ST, Kochetkova M. Breast cancer stem cells and the immune system: promotion, evasion and therapy. J Mammary Gland Biol Neoplasia 2014; 19(2): 203-11.
[68]
Simões BM, Piva M, Iriondo O, et al. Effects of estrogen on the proportion of stem cells in the breast. Breast Cancer Res Treat 2011; 129(1): 23-35.
[69]
Fillmore CM, Gupta PB, Rudnick JA, et al. Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling. Proc Natl Acad Sci USA 2010; 107(50): 21737-42.
[70]
Deng H, Zhang XT, Wang ML, Zheng HY, Liu LJ, Wang ZY. ER-α36-mediated rapid estrogen signaling positively regulates ER-positive breast cancer stem/progenitor cells. PLoS One 2014; 9(2)e88034
[71]
Clayton H, Titley I, Vivanco Md. Growth and differentiation of progenitor/stem cells derived from the human mammary gland. Exp Cell Res 2004; 297(2): 444-60.
[72]
Asselin-Labat ML, Vaillant F, Sheridan JM, et al. Control of mammary stem cell function by steroid hormone signaling. Nature 2010; 465(7299): 798-802.
[73]
Simões BM, Alferez DG, Howell SJ, Clarke RB. The role of steroid hormones in breast cancer stem cells. Endocr Relat Cancer 2015; 22(6): T177-86.
[74]
Ma R, Karthik GM, Lövrot J, et al. Estrogen Receptor β as a Therapeutic Target in Breast Cancer Stem Cells. J Natl Cancer Inst 2017; 109(3): 1-14.
[75]
Asselin-Labat ML, Shackleton M, Stingl J, et al. Steroid hormone receptor status of mouse mammary stem cells. J Natl Cancer Inst 2006; 98(14): 1011-4.
[76]
Horwitz KB, Dye WW, Harrell JC, Kabos P, Sartorius CA. Rare steroid receptor-negative basal-like tumorigenic cells in luminal subtype human breast cancer xenografts. Proc Natl Acad Sci USA 2008; 105(15): 5774-9.
[77]
Raouf A, Zhao Y, et al. Transcriptome analysis of the normal human mammary cell commitment and differentiation process. Cell Stem Cell 2008; 3(1): 109-18.
[78]
Joshi PA, Jackson HW, Beristain AG, et al. Progesterone induces adult mammary stem cell expansion. Nature 2010; 465(7299): 803-7.
[79]
Sartorius CA, Harvell DM, Shen T, Horwitz KB. Progestins initiate a luminal to myoepithelial switch in estrogen-dependent human breast tumors without altering growth. Cancer Res 2005; 65(21): 9779-88.
[80]
Hilton HN, Santucci N, Silvestri A, et al. Progesterone stimulates progenitor cells in normal human breast and breast cancer cells. Breast Cancer Res Treat 2014; 143(3): 423-33.
[81]
Cittelly DM, Finlay-Schultz J, Howe EN, et al. Progestin suppression of miR-29 potentiates dedifferentiation of breast cancer cells via KLF4. Oncogene 2013; 32(20): 2555-64.
[82]
Finlay-Schultz J, Cittelly DM, Hendricks P, et al. Progesterone downregulation of miR-141 contributes to expansion of stem-like breast cancer cells through maintenance of progesterone receptor and Stat5a. Oncogene 2015; 34(28): 3676-87.
[83]
Vares G, Sai S, Wang B, Fujimori A, Nenoi M, Nakajima T. Progesterone generates cancer stem cells through membrane progesterone receptor triggered signaling in basal-like human mammary cells. Cancer Lett 2015; 362(2): 167-73.
[84]
Axlund SD, Yoo BH, Rosen RB, et al. Progesterone-inducible cytokeratin 5-positive cells in luminal breast cancer exhibit progenitor properties. Horm Cancer 2013; 4(1): 36-49.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy