Breast cancer stem cell: the roles and therapeutic implications

Cellular and Molecular Life Sciences

Volumn 74, Issue 6, 2017, Pages 951-966

  Yang, Fang ^a   Xu, Jing ^a   Tang, Lin ^a   Guan, Xiaoxiang ^a  

^a MEDICAL SCHOOL OF NANJING UNIVERSITY   (China)

Author keywords

Biomarker; Epithelial mesenchymal transition; Microenvironment; Signal pathway; Therapy

Indexed keywords

ALPHA6 INTEGRIN; BETA1 INTEGRIN; BETA3 INTEGRIN; BIVATUZUMAB MERTANSINE; CANCER VACCINE; CD133 ANTIGEN; CD24 ANTIGEN; CYTOKERATIN 18; HERMES ANTIGEN; MK 0752; MUCIN 1; N (6,7 DIHYDRO 6 OXO 5H DIBENZ[B,D]AZEPIN 7 YL) 2,2 DIMETHYL N' (2,2,3,3,3 PENTAFLUOROPROPYL)PROPANEDIAMIDE; NIROGACESTAT; OSTEONECTIN; REPARIXIN; STEM CELL ANTIGEN 1; TRANSCRIPTION FACTOR GATA 3; TUMOR MARKER; VANTICTUMAB; VIMENTIN; VISMODEGIB;

ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER GROWTH; CANCER INHIBITION; CANCER STEM CELL; CELL TRANSFORMATION; DRUG RESISTANCE; DRUG TARGETING; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; MESENCHYMAL EPITHELIAL TRANSITION; METASTASIS; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; BIOLOGICAL MODEL; BREAST NEOPLASMS; CARCINOGENESIS; FEMALE; METABOLISM; PATHOLOGY;

ANIMALS; BIOMARKERS, TUMOR; BREAST NEOPLASMS; CARCINOGENESIS; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; HUMANS; MODELS, BIOLOGICAL; NEOPLASTIC STEM CELLS;

EID: 84982124692     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-016-2334-7     Document Type: Review

References (111)

1. Koren S, Bentires-Alj M (2015) Breast tumor heterogeneity: source of fitness. Hurdle for therapy. Mol Cell 60(4):537–546. doi:10.1016/j.molcel.2015.10.031
2. Dawood S, Austin L, Cristofanilli M (2014) Cancer stem cells: implications for cancer therapy. Oncology (Williston Park) 28 (12):1101–1107 (1110)
3. Lawson JC, Blatch GL, Edkins AL (2009) Cancer stem cells in breast cancer and metastasis. Breast Cancer Res Treat 118(2):241–254. doi:10.1007/s10549-009-0524-9
4. 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(7):3983–3988. doi:10.1073/pnas.0530291100
5. Badve S, Nakshatri H (2012) Breast-cancer stem cells-beyond semantics. Lancet Oncol 13(1):e43–e48. doi:10.1016/S1470-2045(11)70191-7
6. Geng SQ, Alexandrou AT, Li JJ (2014) Breast cancer stem cells: multiple capacities in tumor metastasis. Cancer Lett 349(1):1–7. doi:10.1016/j.canlet.2014.03.036
7. Castano Z, Fillmore CM, Kim CF, McAllister SS (2012) The bed and the bugs: interactions between the tumor microenvironment and cancer stem cells. Semin Cancer Biol 22(5–6):462–470. doi:10.1016/j.semcancer.2012.04.006
8. Kreso A, Dick JE (2014) Evolution of the cancer stem cell model. Cell Stem Cell 14(3):275–291. doi:10.1016/j.stem.2014.02.006
9. Skibinski A, Kuperwasser C (2015) The origin of breast tumor heterogeneity. Oncogene 34(42):5309–5316. doi:10.1038/onc.2014.475
10. Martelotto LG, Ng CK, Piscuoglio S, Weigelt B, Reis-Filho JS (2014) Breast cancer intra-tumor heterogeneity. Breast Cancer Res BCR 16(3):210. doi:10.1186/bcr3658
11. Koren S, Reavie L, Couto JP, De Silva D, Stadler MB, Roloff T, Britschgi A, Eichlisberger T, Kohler H, Aina O, Cardiff RD, Bentires-Alj M (2015) PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours. Nature 525(7567):114–118. doi:10.1038/nature14669
12. Louie E, Nik S, Chen JS, Schmidt M, Song B, Pacson C, Chen XF, Park S, Ju J, Chen EI (2010) Identification of a stem-like cell population by exposing metastatic breast cancer cell lines to repetitive cycles of hypoxia and reoxygenation. Breast Cancer Res BCR 12(6):R94. doi:10.1186/bcr2773
13. Fillmore CM, Kuperwasser C (2008) Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res BCR 10(2):R25. doi:10.1186/bcr1982
14. Ahmed MA, Aleskandarany MA, Rakha EA, Moustafa RZ, Benhasouna A, Nolan C, Green AR, Ilyas M, Ellis IO (2012) A CD44(−)/CD24(+) phenotype is a poor prognostic marker in early invasive breast cancer. Breast Cancer Res Treat 133(3):979–995. doi:10.1007/s10549-011-1865-8
15. 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(5):555–567. doi:10.1016/j.stem.2007.08.014
16. 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 BCR 10(1):R10. doi:10.1186/bcr1855
17. 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):62–73. doi:10.1016/j.cell.2009.12.007
18. Vlashi E, Kim K, Lagadec C, Donna LD, McDonald JT, Eghbali M, Sayre JW, Stefani E, McBride W, Pajonk F (2009) In vivo imaging, tracking, and targeting of cancer stem cells. J Natl Cancer Inst 101(5):350–359. doi:10.1093/jnci/djn509
19. Vaillant F, Asselin-Labat ML, Shackleton M, Forrest NC, Lindeman GJ, Visvader JE (2008) The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res 68(19):7711–7717. doi:10.1158/0008-5472.CAN-08-1949
20. Vassilopoulos A, Chisholm C, Lahusen T, Zheng H, Deng CX (2014) A critical role of CD29 and CD49f in mediating metastasis for cancer-initiating cells isolated from a Brca1-associated mouse model of breast cancer. Oncogene 33(47):5477–5482. doi:10.1038/onc.2013.516
21. Wang D, Cai C, Dong X, Yu QC, Zhang XO, Yang L, Zeng YA (2015) Identification of multipotent mammary stem cells by protein C receptor expression. Nature 517(7532):81–84. doi:10.1038/nature13851
22. Grange C, Lanzardo S, Cavallo F, Camussi G, Bussolati B (2008) Sca-1 identifies the tumor-initiating cells in mammary tumors of BALB-neuT transgenic mice. Neoplasia 10(12):1433–1443
23. 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(7):2419–2426. doi:10.1158/0008-5472.CAN-07-2249
24. Cho RW, Wang X, Diehn M, Shedden K, Chen GY, Sherlock G, Gurney A, Lewicki J, Clarke MF (2008) Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors. Stem Cells 26(2):364–371. doi:10.1634/stemcells.2007-0440
25. Park SY, Lee HE, Li H, Shipitsin M, Gelman R, Polyak K (2010) Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res 16(3):876–887. doi:10.1158/1078-0432.CCR-09-1532
26. Oakes SR, Gallego-Ortega D, Ormandy CJ (2014) The mammary cellular hierarchy and breast cancer. Cell Mol Life Sci CMLS 71(22):4301–4324. doi:10.1007/s00018-014-1674-4
27. Hwang-Verslues WW, Kuo WH, Chang PH, Pan CC, Wang HH, Tsai ST, Jeng YM, Shew JY, Kung JT, Chen CH, Lee EY, Chang KJ, Lee WH (2009) Multiple lineages of human breast cancer stem/progenitor cells identified by profiling with stem cell markers. PLoS One 4(12):e8377. doi:10.1371/journal.pone.0008377
28. Tsang JY, Huang YH, Luo MH, Ni YB, Chan SK, Lui PC, Yu AM, Tan PH, Tse GM (2012) Cancer stem cell markers are associated with adverse biomarker profiles and molecular subtypes of breast cancer. Breast Cancer Res Treat 136(2):407–417. doi:10.1007/s10549-012-2271-6
29. Bensimon J, Altmeyer-Morel S, Benjelloun H, Chevillard S, Lebeau J (2013) CD24(−/low) stem-like breast cancer marker defines the radiation-resistant cells involved in memorization and transmission of radiation-induced genomic instability. Oncogene 32(2):251–258. doi:10.1038/onc.2012.31
30. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3(7):730–737
31. Liu S, Cong Y, Wang D, Sun Y, Deng L, Liu Y, Martin-Trevino R, Shang L, McDermott SP, Landis MD, Hong S, Adams A, D’Angelo R, Ginestier C, Charafe-Jauffret E, Clouthier SG, Birnbaum D, Wong ST, Zhan M, Chang JC, Wicha MS (2014) Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts. Stem Cell Rep 2(1):78–91. doi:10.1016/j.stemcr.2013.11.009
32. Ping YF, Bian XW (2011) Consice review: contribution of cancer stem cells to neovascularization. Stem Cells 29(6):888–894. doi:10.1002/stem.650
33. Brooks MD, Burness ML, Wicha MS (2015) Therapeutic implications of cellular heterogeneity and plasticity in breast cancer. Cell Stem Cell 17(3):260–271. doi:10.1016/j.stem.2015.08.014
34. Zhou L, Jiang Y, Yan T, Di G, Shen Z, Shao Z, Lu J (2010) The prognostic role of cancer stem cells in breast cancer: a meta-analysis of published literatures. Breast Cancer Res Treat 122(3):795–801. doi:10.1007/s10549-010-0999-4
35. Morrison BJ, Schmidt CW, Lakhani SR, Reynolds BA, Lopez JA (2008) Breast cancer stem cells: implications for therapy of breast cancer. Breast Cancer Res BCR 10(4):210. doi:10.1186/bcr2111
36. Lynch MD, Cariati M, Purushotham AD (2006) Breast cancer, stem cells and prospects for therapy. Breast Cancer Res BCR 8(3):211. doi:10.1186/bcr1513
37. Schneider MR, Yarden Y (2016) The EGFR–HER2 module: a stem cell approach to understanding a prime target and driver of solid tumors. Oncogene 35(23):2949–2960. doi:10.1038/onc.2015.372
38. Luo M, Brooks M, Wicha MS (2015) Epithelial–mesenchymal plasticity of breast cancer stem cells: implications for metastasis and therapeutic resistance. Curr Pharm Des 21(10):1301–1310
39. Asiedu MK, Beauchamp-Perez FD, Ingle JN, Behrens MD, Radisky DC, Knutson KL (2014) AXL induces epithelial-to-mesenchymal transition and regulates the function of breast cancer stem cells. Oncogene 33(10):1316–1324. doi:10.1038/onc.2013.57
40. Mani SA, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N, Kutok JL, Hartwell K, Richardson AL, Weinberg RA (2007) Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci USA 104(24):10069–10074. doi:10.1073/pnas.0703900104
41. Liang Y, Hu J, Li J, Liu Y, Yu J, Zhuang X, Mu L, Kong X, Hong D, Yang Q, Hu G (2015) Epigenetic activation of TWIST1 by MTDH promotes cancer stem-like cell traits in breast cancer. Cancer Res 75(17):3672–3680. doi:10.1158/0008-5472.CAN-15-0930
42. May CD, Sphyris N, Evans KW, Werden SJ, Guo W, Mani SA (2011) Epithelial–mesenchymal transition and cancer stem cells: a dangerously dynamic duo in breast cancer progression. Breast Cancer Res BCR 13(1):202. doi:10.1186/bcr2789
43. Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF (2007) The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med 356(3):217–226. doi:10.1056/NEJMoa063994
44. Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G, Datar RH, Cote RJ (2006) Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res 12(19):5615–5621. doi:10.1158/1078-0432.CCR-06-0169
45. Liu H, Patel MR, Prescher JA, Patsialou A, Qian D, Lin J, Wen S, Chang YF, Bachmann MH, Shimono Y, Dalerba P, Adorno M, Lobo N, Bueno J, Dirbas FM, Goswami S, Somlo G, Condeelis J, Contag CH, Gambhir SS, Clarke MF (2010) Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proc Natl Acad Sci USA 107(42):18115–18120. doi:10.1073/pnas.1006732107
46. Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, Hur MH, Diebel ME, Monville F, Dutcher J, Brown M, Viens P, Xerri L, Bertucci F, Stassi G, Dontu G, Birnbaum D, Wicha MS (2009) Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res 69(4):1302–1313. doi:10.1158/0008-5472.CAN-08-2741
47. Samanta D, Gilkes DM, Chaturvedi P, Xiang L, Semenza GL (2014) Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells. Proc Natl Acad Sci USA 111(50):E5429–E5438. doi:10.1073/pnas.1421438111
48. 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(9):672–679. doi:10.1093/jnci/djn123
49. Phillips TM, McBride WH, Pajonk F (2006) The response of CD24(−/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst 98(24):1777–1785. doi:10.1093/jnci/djj495
50. Piva M, Domenici G, Iriondo O, Rabano M, Simoes BM, Comaills V, Barredo I, Lopez-Ruiz JA, Zabalza I, Kypta R, Vivanco M (2014) Sox2 promotes tamoxifen resistance in breast cancer cells. EMBO Mol Med 6(1):66–79. doi:10.1002/emmm.201303411
51. Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, Fan C, Zhang X, He X, Pavlick A, Gutierrez MC, Renshaw L, Larionov AA, Faratian D, Hilsenbeck SG, Perou CM, Lewis MT, Rosen JM, Chang JC (2009) Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 106(33):13820–13825. doi:10.1073/pnas.0905718106
52. Wang X, Jung YS, Jun S, Lee S, Wang W, Schneider A, Sun OhY, Lin SH, Park BJ, Chen J, Keyomarsi K, Park JI (2016) PAF-Wnt signaling-induced cell plasticity is required for maintenance of breast cancer cell stemness. Nat Commun 7:10633. doi:10.1038/ncomms10633
53. Miele L, Golde T, Osborne B (2006) Notch signaling in cancer. Curr Mol Med 6(8):905–918
54. D’Angelo RC, Ouzounova M, Davis A, Choi D, Tchuenkam SM, Kim G, Luther T, Quraishi AA, Senbabaoglu Y, Conley SJ, Clouthier SG, Hassan KA, Wicha MS, Korkaya H (2015) Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity. Mol Cancer Ther 14(3):779–787. doi:10.1158/1535-7163.MCT-14-0228
55. Mamaeva V, Niemi R, Beck M, Ozliseli E, Desai D, Landor S, Gronroos T, Kronqvist P, Pettersen IK, McCormack E, Rosenholm JM, Linden M, Sahlgren C (2016) Inhibiting notch activity in breast cancer stem cells by glucose functionalized nanoparticles carrying gamma-secretase inhibitors. Mol Ther 24(5):926–936. doi:10.1038/mt.2016.42
56. McGowan PM, Simedrea C, Ribot EJ, Foster PJ, Palmieri D, Steeg PS, Allan AL, Chambers AF (2011) Notch1 inhibition alters the CD44hi/CD24lo population and reduces the formation of brain metastases from breast cancer. Mol Cancer Res MCR 9(7):834–844. doi:10.1158/1541-7786.MCR-10-0457
57. Schott AF, Landis MD, Dontu G, Griffith KA, Layman RM, Krop I, Paskett LA, Wong H, Dobrolecki LE, Lewis MT, Froehlich AM, Paranilam J, Hayes DF, Wicha MS, Chang JC (2013) Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors. Clin Cancer Res 19(6):1512–1524. doi:10.1158/1078-0432.CCR-11-3326
58. Krop I, Demuth T, Guthrie T, Wen PY, Mason WP, Chinnaiyan P, Butowski N, Groves MD, Kesari S, Freedman SJ, Blackman S, Watters J, Loboda A, Podtelezhnikov A, Lunceford J, Chen C, Giannotti M, Hing J, Beckman R, Lorusso P (2012) Phase I pharmacologic and pharmacodynamic study of the gamma secretase (Notch) inhibitor MK-0752 in adult patients with advanced solid tumors. J Clin Oncol 30(19):2307–2313. doi:10.1200/JCO.2011.39.1540
59. Niehrs C (2012) The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol 13(12):767–779. doi:10.1038/nrm3470
60. Jang GB, Hong IS, Kim RJ, Lee SY, Park SJ, Lee ES, Park JH, Yun CH, Chung JU, Lee KJ, Lee HY, Nam JS (2015) Wnt/beta-catenin small-molecule inhibitor CWP232228 preferentially inhibits the growth of breast cancer stem-like cells. Cancer Res 75(8):1691–1702. doi:10.1158/0008-5472.CAN-14-2041
61. Lamb R, Ablett MP, Spence K, Landberg G, Sims AH, Clarke RB (2013) Wnt pathway activity in breast cancer sub-types and stem-like cells. PLoS One 8(7):e67811. doi:10.1371/journal.pone.0067811
62. Xu J, Prosperi JR, Choudhury N, Olopade OI, Goss KH (2015) Beta-catenin is required for the tumorigenic behavior of triple-negative breast cancer cells. PLoS One 10(2):e0117097. doi:10.1371/journal.pone.0117097
63. Xu L, Zhang L, Hu C, Liang S, Fei X, Yan N, Zhang Y, Zhang F (2016) WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells. Int J Oncol 48(3):1175–1186. doi:10.3892/ijo.2016.3337
64. Fu Y, Chang H, Peng X, Bai Q, Yi L, Zhou Y, Zhu J, Mi M (2014) Resveratrol inhibits breast cancer stem-like cells and induces autophagy via suppressing Wnt/beta-catenin signaling pathway. PLoS One 9(7):e102535. doi:10.1371/journal.pone.0102535
65. Briscoe J, Therond PP (2013) The mechanisms of hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol 14(7):416–429. doi:10.1038/nrm3598
66. Wang L, Duan W, Kang L, Mao J, Yu X, Fan S, Li L, Tao Y (2014) Smoothened activates breast cancer stem-like cell and promotes tumorigenesis and metastasis of breast cancer. Biomed Pharmacother 68(8):1099–1104. doi:10.1016/j.biopha.2014.09.012
67. Sims-Mourtada J, Opdenaker LM, Davis J, Arnold KM, Flynn D (2015) Taxane-induced hedgehog signaling is linked to expansion of breast cancer stem-like populations after chemotherapy. Mol Carcinog 54(11):1480–1493. doi:10.1002/mc.22225
68. Kotiyal S, Bhattacharya S (2014) Breast cancer stem cells, EMT and therapeutic targets. Biochem Biophys Res Commun 453(1):112–116. doi:10.1016/j.bbrc.2014.09.069
69. Kise K, Kinugasa-Katayama Y, Takakura N (2016) Tumor microenvironment for cancer stem cells. Adv Drug Deliv Rev 99(Pt B):197–205. doi:10.1016/j.addr.2015.08.005
70. Korkaya H, Liu S, Wicha MS (2011) Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Investig 121(10):3804–3809. doi:10.1172/JCI57099
71. Plaks V, Kong N, Werb Z (2015) The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell 16(3):225–238. doi:10.1016/j.stem.2015.02.015
72. Xie J, Xiao Y, Zhu XY, Ning ZY, Xu HF, Wu HM (2016) Hypoxia regulates stemness of breast cancer MDA-MB-231 cells. Med Oncol 33(5):42. doi:10.1007/s12032-016-0755-7
73. Iriondo O, Rabano M, Domenici G, Carlevaris O, Lopez-Ruiz JA, Zabalza I, Berra E, Vivanco M (2015) Distinct breast cancer stem/progenitor cell populations require either HIF1alpha or loss of PHD3 to expand under hypoxic conditions. Oncotarget 6(31):31721–31739. doi:10.18632/oncotarget.5564
74. Mathieu J, Zhang Z, Zhou W, Wang AJ, Heddleston JM, Pinna CM, Hubaud A, Stadler B, Choi M, Bar M, Tewari M, Liu A, Vessella R, Rostomily R, Born D, Horwitz M, Ware C, Blau CA, Cleary MA, Rich JN, Ruohola-Baker H (2011) HIF induces human embryonic stem cell markers in cancer cells. Cancer Res 71(13):4640–4652. doi:10.1158/0008-5472.CAN-10-3320
75. Zhang C, Samanta D, Lu H, Bullen JW, Zhang H, Chen I, He X, Semenza GL (2016) Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. Proc Natl Acad Sci USA. doi:10.1073/pnas.1602883113
76. Ma F, Chen D, Chen F, Chi Y, Han Z, Feng X, Li X, Han Z (2015) Human umbilical cord mesenchymal stem cells promote breast cancer metastasis by interleukin-8- and interleukin-6-dependent induction of CD44(+)/CD24(−) cells. Cell Transplant 24(12):2585–2599. doi:10.3727/096368915X687462
77. Kim SY, Kang JW, Song X, Kim BK, Yoo YD, Kwon YT, Lee YJ (2013) Role of the IL-6–JAK1–STAT3–Oct-4 pathway in the conversion of non-stem cancer cells into cancer stem-like cells. Cell Signal 25(4):961–969. doi:10.1016/j.cellsig.2013.01.007
78. Iliopoulos D, Hirsch HA, Wang G, Struhl K (2011) Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc Natl Acad Sci USA 108(4):1397–1402. doi:10.1073/pnas.1018898108
79. Buess M, Rajski M, Vogel-Durrer BM, Herrmann R, Rochlitz C (2009) Tumor-endothelial interaction links the CD44(+)/CD24(−) phenotype with poor prognosis in early-stage breast cancer. Neoplasia 11(10):987–1002
80. Lohela M, Casbon AJ, Olow A, Bonham L, Branstetter D, Weng N, Smith J, Werb Z (2014) Intravital imaging reveals distinct responses of depleting dynamic tumor-associated macrophage and dendritic cell subpopulations. Proc Natl Acad Sci USA 111(47):E5086–E5095. doi:10.1073/pnas.1419899111
81. Casbon AJ, Reynaud D, Park C, Khuc E, Gan DD, Schepers K, Passegue E, Werb Z (2015) Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils. Proc Natl Acad Sci USA 112(6):E566–E575. doi:10.1073/pnas.1424927112
82. Yang J, Liao D, Chen C, Liu Y, Chuang TH, Xiang R, Markowitz D, Reisfeld RA, Luo Y (2013) Tumor-associated macrophages regulate murine breast cancer stem cells through a novel paracrine EGFR/Stat3/Sox-2 signaling pathway. Stem Cells 31(2):248–258. doi:10.1002/stem.1281
83. Okuda H, Kobayashi A, Xia B, Watabe M, Pai SK, Hirota S, Xing F, Liu W, Pandey PR, Fukuda K, Modur V, Ghosh A, Wilber A, Watabe K (2012) Hyaluronan synthase HAS2 promotes tumor progression in bone by stimulating the interaction of breast cancer stem-like cells with macrophages and stromal cells. Cancer Res 72(2):537–547. doi:10.1158/0008-5472.CAN-11-1678
84. Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL (1996) Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56(20):4625–4629
85. Leek RD, Harris AL (2002) Tumor-associated macrophages in breast cancer. J Mammary Gland Biol Neoplasia 7(2):177–189
86. Smith AL, Robin TP, Ford HL (2012) Molecular pathways: targeting the TGF-beta pathway for cancer therapy. Clin Cancer Res 18(17):4514–4521. doi:10.1158/1078-0432.CCR-11-3224
87. Cabarcas SM, Mathews LA, Farrar WL (2011) The cancer stem cell niche–there goes the neighborhood? Int J Cancer (J Int Cancer) 129(10):2315–2327. doi:10.1002/ijc.26312
88. Liu F, Lang R, Zhao J, Zhang X, Pringle GA, Fan Y, Yin D, Gu F, Yao Z, Fu L (2011) CD8(+) cytotoxic T cell and FOXP3(+) regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes. Breast Cancer Res Treat 130(2):645–655. doi:10.1007/s10549-011-1647-3
89. Seo AN, Lee HJ, Kim EJ, Kim HJ, Jang MH, Lee HE, Kim YJ, Kim JH, Park SY (2013) Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for pathological complete response to primary systemic therapy in breast cancer. Br J Cancer 109(10):2705–2713. doi:10.1038/bjc.2013.634
90. Lu P, Weaver VM, Werb Z (2012) The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol 196(4):395–406. doi:10.1083/jcb.201102147
91. Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, Zanconato F, Le Digabel J, Forcato M, Bicciato S, Elvassore N, Piccolo S (2011) Role of YAP/TAZ in mechanotransduction. Nature 474(7350):179–183. doi:10.1038/nature10137
92. Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M, Parenti AR, Poletti A, Daidone MG, Dupont S, Basso G, Bicciato S, Piccolo S (2011) The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 147(4):759–772. doi:10.1016/j.cell.2011.09.048
93. Liu B, Sun L, Song E (2013) Non-coding RNAs regulate tumor cell plasticity. Sci China Life Sci 56(10):886–890. doi:10.1007/s11427-013-4554-5
94. Shimono Y, Mukohyama J, Nakamura S, Minami H (2015) MicroRNA regulation of human breast cancer stem cells. J Clin Med. doi:10.3390/jcm5010002
95. Tekiner TA, Basaga H (2013) Role of microRNA deregulation in breast cancer cell chemoresistance and stemness. Curr Med Chem 20(27):3358–3369
96. Xu C, Sun X, Qin S, Wang H, Zheng Z, Xu S, Luo G, Liu P, Liu J, Du N, Zhang Y, Liu D, Ren H (2015) Let-7a regulates mammosphere formation capacity through Ras/NF-kappaB and Ras/MAPK/ERK pathway in breast cancer stem cells. Cell Cycle 14(11):1686–1697. doi:10.1080/15384101.2015.1030547
97. Bahena-Ocampo I, Espinosa M, Ceballos-Cancino G, Lizarraga F, Campos-Arroyo D, Schwarz A, Maldonado V, Melendez-Zajgla J (2016) miR-10b expression in breast cancer stem cells supports self-renewal through negative PTEN regulation and sustained AKT activation. EMBO Rep 17(5):648–658. doi:10.15252/embr.201540678
98. Li H, Zhu L, Xu L, Qin K, Liu C, Yu Y, Su D, Wu K, Sheng Y (2015) Long noncoding RNA linc00617 exhibits oncogenic activity in breast cancer. Mol Carcinog. doi:10.1002/mc.22338
99. Zhou M, Hou Y, Yang G, Zhang H, Tu G, Du YE, Wen S, Xu L, Tang X, Tang S, Yang L, Cui X, Liu M (2016) LncRNA-Hh strengthen cancer stem cells generation in twist-positive breast cancer via activation of hedgehog signaling pathway. Stem Cells 34(1):55–66. doi:10.1002/stem.2219
100. Rupp U, Schoendorf-Holland E, Eichbaum M, Schuetz F, Lauschner I, Schmidt P, Staab A, Hanft G, Huober J, Sinn HP, Sohn C, Schneeweiss A (2007) Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: final results of a phase I study. Anticancer Drugs 18(4):477–485. doi:10.1097/CAD.0b013e32801403f4
101. Fillmore CM, Gupta PB, Rudnick JA, Caballero S, Keller PJ, Lander ES, Kuperwasser C (2010) Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling. Proc Natl Acad Sci USA 107(50):21737–21742. doi:10.1073/pnas.1007863107
102. Schramek D, Leibbrandt A, Sigl V, Kenner L, Pospisilik JA, Lee HJ, Hanada R, Joshi PA, Aliprantis A, Glimcher L, Pasparakis M, Khokha R, Ormandy CJ, Widschwendter M, Schett G, Penninger JM (2010) Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature 468(7320):98–102. doi:10.1038/nature09387
103. Karthik GM, Ma R, Lovrot J, Kis LL, Lindh C, Blomquist L, Fredriksson I, Bergh J, Hartman J (2015) mTOR inhibitors counteract tamoxifen-induced activation of breast cancer stem cells. Cancer Lett 367(1):76–87. doi:10.1016/j.canlet.2015.07.017
104. Lamb R, Lehn S, Rogerson L, Clarke RB, Landberg G (2013) Cell cycle regulators cyclin D1 and CDK4/6 have estrogen receptor-dependent divergent functions in breast cancer migration and stem cell-like activity. Cell Cycle 12(15):2384–2394. doi:10.4161/cc.25403
105. Nair R, Roden DL, Teo WS, McFarland A, Junankar S, Ye S, Nguyen A, Yang J, Nikolic I, Hui M, Morey A, Shah J, Pfefferle AD, Usary J, Selinger C, Baker LA, Armstrong N, Cowley MJ, Naylor MJ, Ormandy CJ, Lakhani SR, Herschkowitz JI, Perou CM, Kaplan W, O’Toole SA, Swarbrick A (2014) c-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer. Oncogene 33(30):3992–4002. doi:10.1038/onc.2013.368
106. Diessner J, Bruttel V, Stein RG, Horn E, Hausler SF, Dietl J, Honig A, Wischhusen J (2014) Targeting of preexisting and induced breast cancer stem cells with trastuzumab and trastuzumab emtansine (T-DM1). Cell Death Dis 5:e1149. doi:10.1038/cddis.2014.115
107. Singh JK, Farnie G, Bundred NJ, Simoes BM, Shergill A, Landberg G, Howell SJ, Clarke RB (2013) Targeting CXCR1/2 significantly reduces breast cancer stem cell activity and increases the efficacy of inhibiting HER2 via HER2-dependent and -independent mechanisms. Clin Cancer Res 19(3):643–656. doi:10.1158/1078-0432.CCR-12-1063
108. Idowu MO, Kmieciak M, Dumur C, Burton RS, Grimes MM, Powers CN, Manjili MH (2012) 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 43(3):364–373. doi:10.1016/j.humpath.2011.05.005
109. Guo W, Keckesova Z, Donaher JL, Shibue T, Tischler V, Reinhardt F, Itzkovitz S, Noske A, Zurrer-Hardi U, Bell G, Tam WL, Mani SA, van Oudenaarden A, Weinberg RA (2012) Slug and Sox9 cooperatively determine the mammary stem cell state. Cell 148(5):1015–1028. doi:10.1016/j.cell.2012.02.008
110. Klevebring D, Rosin G, Ma R, Lindberg J, Czene K, Kere J, Fredriksson I, Bergh J, Hartman J (2014) Sequencing of breast cancer stem cell populations indicates a dynamic conversion between differentiation states in vivo. Breast Cancer Res BCR 16(4):R72. doi:10.1186/bcr3687
111. Leder K, Holland EC, Michor F (2010) The therapeutic implications of plasticity of the cancer stem cell phenotype. PLoS One 5(12):e14366. doi:10.1371/journal.pone.0014366