乳腺癌干细胞抵抗放射治疗及化疗的调控机制
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摘要
据中国城市癌症报告统计,乳腺癌是中国城市女性发病率最高的癌症。尽管乳腺癌早期原位切除及放射治疗和化疗(简称放化疗)后,患者的5年和10年生存率较好,但依旧有小部分癌细胞逃逸、潜伏和扩散,导致乳腺癌复发和转移。未治愈乳腺癌中,约70%发生肺转移,60%发生骨转移和肝转移,15%发生脑转移。肿瘤干细胞是肿瘤组织中存在的少量具有干细胞特征的细胞亚群,有极强的再生肿瘤能力以及天然放化疗抵抗能力,被视作乳腺癌复发、转移的主要原因。靶向肿瘤干细胞的研究,为人类彻底攻克恶性肿瘤带来了希望。乳腺癌组织中具备乙醛脱氢酶(+)、CD44~+ CD24~-Lin~-等特征的细胞亚群已经被证实是乳腺肿瘤干细胞。笔者总结了乳腺肿瘤干细胞的鉴定、起源、特征、调控机制、放化疗不敏感的原因及临床靶向治疗的研究进展,供同行参考。
According to the statistic data of cancer in China, breast cancer has the highest incidence in female residents in cities of China. Although the traditional therapies, including surgery, radiation therapy, chemotherapy and hormone therapy have led to the increased 5-year and 10-year survival, there are still a small number of cancer cells survived from treatment, causing cancer recurrence and/or metastasis. Around 70% of survived breast cancer can metastasize to the lung, 60% to the bone and liver and 15% to the brain. Breast cancer stem cells, a subpopulation of breast cancer cells carrying stem cell properties, have strong ability to regenerate tumor and natural resistance to radiation and chemotherapy, which may be responsible for cancer recurrence and metastasis. The strategies targeting at cancer stem cell bring new hope for the treatment of cancer in the near future. In human breast cancer tissues, ALDH positive cells and CD44~+CD24~-Lin~- cells have been identified as breast cancer stem cells. In this review, we discussed the identification, origin, properties, regulatory mechanism of breast cancer stem cells and the resistance against radiation and chemotherapy, as well as the advances of clinical targeted therapy.
According to the statistic data of cancer in China, breast cancer has the highest incidence in female residents in cities of China. Although the traditional therapies, including surgery, radiation therapy, chemotherapy and hormone therapy have led to the increased 5-year and 10-year survival, there are still a small number of cancer cells survived from treatment, causing cancer recurrence and/or metastasis. Around 70% of survived breast cancer can metastasize to the lung, 60% to the bone and liver and 15% to the brain. Breast cancer stem cells, a subpopulation of breast cancer cells carrying stem cell properties, have strong ability to regenerate tumor and natural resistance to radiation and chemotherapy, which may be responsible for cancer recurrence and metastasis. The strategies targeting at cancer stem cell bring new hope for the treatment of cancer in the near future. In human breast cancer tissues, ALDH positive cells and CD44~+CD24~-Lin~- cells have been identified as breast cancer stem cells. In this review, we discussed the identification, origin, properties, regulatory mechanism of breast cancer stem cells and the resistance against radiation and chemotherapy, as well as the advances of clinical targeted therapy.
引文
[1] Chen W, Zheng R, Zhang S, et al. Cancer incidence and mortality in China in 2013: an analysis based on urbanization level [J]. Chin J Cancer Res, 2017, 29(1):1-10.
[2] 赵晶, 付丽. 乳腺癌的分子分型 [J/CD]. 中华乳腺病杂志(电子版),2009, 3 (2):195-203.
[3] Oei AL, Vriend LE, Krawczyk PM, et al. Targeting therapy-resistant cancer stem cells by hyperthermia [EB/OL]. [2018-02-10]. https://www.tandfonline.com/doi/full/10.1080/02656736.2017.1279757.
[4] Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest [J]. 2011, 121(10):3804-9.
[5] 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 [J]. Cell Stem Cell, 2007, 1(5):555-567.
[6] Shima H, Yamada A, Ishikawa T, et al. Are breast cancer stem cells the key to resolving clinical issues in breast cancer therapy?[J]. Gland Surg, 2017, 6(1):82-88.
[7] Porkka K, Blomqvist C, Rissanen P, et al. Salvage therapies in women who fail to respond to first-line treatment with fluorouracil, epirubicin, and cyclophosphamide for advanced breast cancer [J]. J Clin Oncol, 1994, 12(8):1639-1647.
[8] Hara T, Iwadate M, Tachibana K, et al. Metastasis of breast cancer cells to the bone, lung, and lymph nodes promotes resistance to ionizing radiation [J]. Strahlenther Onkol, 2017, 193(10):848-855.
[9] Dontu G, Abdallah WM, Foley JM, et al. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells [J]. Genes Dev, 2003, 17(10):1253-1270.
[10] Dou J, Pan M, Wen P, et al. Isolation and identification of cancer stem-like cells from murine melanoma cell lines[J]. Cell Mol Immunol, 2007, 4(6):467-472.
[11] Marsden CG, Wright MJ, Pochampally R, et al. Breast tumor-initiating cells isolated from patient core biopsies for study of hormone action[J]. Methods Mol Biol, 2009, 590:363-375.
[12] Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice [J]. Nature, 1994, 367(6464):645-648.
[13] Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells [J]. Proc Natl Acad Sci USA, 2003, 100(7):3983-3988.
[14] Kanwal R, Shukla S, Walker E, et al. Acquisition of tumorigenic potential and therapeutic resistance in CD133+ subpopulation of prostate cancer cells exhibiting stem-cell like characteristics [J]. Cancer Lett, 2018,430:25-33.
[15] Satar NA, Fakiruddin KS, Lim MN, et al. Novel triplepositive markers identified in human nonsmall cell lung cancer cell line with chemotherapy-resistant and putative cancer stem cell characteristics [J]. Oncol Rep, 2018, 40(2):669-681.
[16] Patel SA, Ndabahaliye A, Lim PK, et al. Challenges in the development of future treatments for breast cancer stem cells [J]. Breast Cancer (Dove Med Press), 2010, 2:1-11.
[17] Ricardo S, Vieira AF, Gerhard R, et al. Breast cancer stem cell markers CD44, CD24 and ALDH1:expression distribution within intrinsic molecular subtype [J]. J Clin Pathol, 2011,64(11):937-946.
[18] Honeth G, Bendahl PO, Ringnér M, et al. The CD44+/CD24- phenotype is enriched in basal-like breast tumors [J]. Breast Cancer Res, 2008, 10(3):R53.
[19] Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct “side population” of cells with high drug efflux capacity in human tumor cells [J]. Proc Natl Acad Sci USA, 2004, 101(39):14 228-14 233.
[20] Nakanishi T, Chumsri S, Khakpour N, et al. Side-population cells in luminal-type breast cancer have tumour initiating cell properties, and are regulated by HER-2 expression and signaling [J]. Br J Cancer, 2010, 102(5):815-826.
[21] Charafe-Jauffret E, Ginestier C, Iovino F, et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature [J].Cancer Res,2009,69(4):1302-1313.
[22] Wright MH, Calcagno AM, Salcido CD, et al. Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics [J]. Breast Cancer Res, 2008,10(1):R10.
[23] 肖锡岗, 房林. 乳腺肿瘤干细胞筛选方法和治疗抵抗研究进展 [J/CD].中华乳腺病杂志(电子版), 2010, 4(3):329-338.
[24] Sarkar P, Basu K, Sarkar P, et al. Correlations of aldehyde dehydrogenase-1 (ALDH1) expression with traditional prognostic parameters and different molecular subtypes of breast carcinoma [J]. Clujul Med, 2018,91(2):181-187.
[25] Mansour SF, Atwa MM. Clinicopathological significance of CD133 and ALDH1 cancer stem cell marker expression in invasive ductal breast carcinoma [J]. Asian Pac J Cancer Prev, 2015,16(17):7491-7496.
[26] Liu S, Cong Y, Wang D, et al. Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts[J]. Stem Cell Reports, 2013, 2(1):78-91.
[27] Hartwig FP, Nedel F, Collares T, et al. Oncogenic somatic events in tissue-specific stem cells: a role in cancer recurrence?[J]. Ageing Res Rev, 2014,13:100-106.
[28] Zhang M, Lee AV, Rosen JM. The cellular origin and evolution of breast cancer [J]. Cold Spring Harb Perspect Med, 2017, 7(3). pii: a027128.
[29] Kotiyal S, Bhattacharya S. Breast cancer stem cells, EMT and therapeutic targets [J]. Biochem Biophys Res Commun, 2014, 453(1):112-116.
[30] Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells [J]. Cell, 2008, 133(4):704-715.
[31] Lim E, Vaillant F, Wu D, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers [J]. Nat Med, 2009,15(8):907-913.
[32] Shackleton M, Vaillant F, Simpson KJ, et al.Generation of a functional mammary gland from a single stem cell [J]. Nature, 2006, 439(7072):84-88.
[33] Brooks MD, Wicha MS. Tumor twitter: cellular communication in the breast cancer stem cell niche [J]. Cancer Discov, 2015, 5(5):469-471.
[34] Korkaya H, Kim GI, Davis A, et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER-2+ breast cancer by expanding the cancer stem cell population [J]. Mol Cell, 2012, 47(4):570-584.
[35] Bhola NE, Balko JM, Dugger TC, et al. TGF-beta inhibition enhances chemotherapy action against triple negative breast cancer [J]. J Clin Invest, 2013, 123(3):1348-1358.
[36] Singh JK, Sim?es BM, Howell SJ, et al. Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells [J]. Breast Cancer Res, 2013, 15(4):210.
[37] Jang GB, Hong IS, Kim RJ, et al. Wnt/β-catenin small-molecule inhibitor CWP232228 preferentially inhibits the growth of breast cancer stem-like cells [J]. Cancer Res, 2015, 75(8):1691-1702.
[38] Baker A, Wyatt D, Bocchetta M, et al. Notch-1-PTEN-ERK1/2 signaling axis promotes HER-2+ breast cancer cell proliferation and stem cell survival [J]. Oncogene, 2018, 37(33):4489-4504.
[39] Harrison H, Farnie G, Howell SJ, et al. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor [J]. Cancer Res, 2010,70(2):709-718.
[40] Wang D, Xu J, Liu B, et al. IL6 blockade potentiates the anti-tumor effects of γ-secretase inhibitors in Notch3-expressing breast cancer [J]. Cell Death Differ, 2018, 25(2):330-339.
[41] Zhou M, Hou Y, Yang G, et al. LncRNA-Hh strengthen cancer stem cells generation in twist-positive breast cancer via activation of Hedgehog signaling pathway [J]. Stem Cells, 2016, 34(1):55-56.
[42] Ramaswamy B, Lu Y, Teng KY, et al. Hedgehog signaling is a novel therapeutic target in tamoxifen-resistant breast cancer aberrantly activated by PI3K/AKT pathway [J]. Cancer Res, 2012, 72(19):5048-5059.
[43] Al-Ejeh F, Smart CE, Morrison BJ, et al. Breast cancer stem cells: treatment resistance and therapeutic opportunities [J]. Carcinogenesis, 2011, 32(5):650-658.
[44] Morrison BJ, Schmidt CW, Lakhani SR, et al. Breast cancer stem cells: implications for therapy of breast cancer [J]. Breast Cancer Res, 2008, 10(4):210.
[45] Rycaj K, Tang DG. Cancer stem cells and radioresistance [J]. Int J Radiat Biol, 2014,90(8):615-621.
[46] Vasiliou V, Vasiliou K, Nebert DW. Human ATP-binding cassette (ABC) transporter family [J]. Hum Genomics, 2009, 3(3):281-290.
[47] Leonard GD, Fojo T, Bates SE. The role of ABC transporters in clinical practice [J]. Oncologist, 2003, 8(5):411-424.
[48] Ma I, Allan AL. The role of human aldehyde dehydrogenase in normal and cancer stem cells [J]. Stem Cell Rev, 2011, 7(2):292-306.
[49] Young SZ, Bordey A. GABA’s control of stem and cancer cell proliferation in adult neural and peripheral niches [J]. Physiology (Bethesda), 2009, 24: 171-185.
[50] Tanei T, Morimoto K, Shimazu K, et al. Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential paclitaxel and epirubicin-based chemotherapy for breast cancers [J]. Clin Cancer Res, 2009,15(12):4234-4241.
[51] Singh S, Brocker C, Koppaka V, et al. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress [J]. Free Radic Biol Med, 2013, 56: 89-101.
[52] Woodward WA, Chen MS, Behbod F, et al. WNT/β-catenin mediates radiation resistance of mouse mammary progenitor cells [J]. Proc Natl Acad Sci U S A, 2007, 104(2):618-623.
[53] Munzone E, Colleoni M. Optimal management of luminal breast cancer: how much endocrine therapy is long enough? [J]. Ther Adv Med Oncol, 2018, 10:1-11.
[54] Sansone P, Berishaj M, Rajasekhar VK, et al. Evolution of cancer stem-like cells in endocrine-resistant metastatic breast cancers is mediated by stromal microvesicles [J]. Cancer Res, 2017, 77(8):1927-1941.
[55] Sim?es BM, Piva M, Iriondo O, et al. Effects of estrogen on the proportion of stem cells in the breast [J]. Breast Cancer Res Treat, 2011, 129(1):23-35.
[56] Leung EY, Askarian-Amiri ME, Sarkar D, et al. Endocrine therapy of estrogen receptor-positive breast cancer cells: early differential effects on stem cell markers [J]. Front Oncol, 2017,7:184.
[57] Bozorgi A, Khazaei M, Khazaei MR. New findings on breast cancer stem cells:a review [J]. J Breast Cancer, 2015,18(4):303-312.
[58] Ginestier C, Liu S, Diebel ME, et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts [J]. J Clin Invest, 2010, 120(2):485-497.
[59] Yin H, Glass J. The phenotypic radiation resistance of CD44+/CD24(-or low) breast cancer cells is mediated through the enhanced activation of ATM signaling [J]. PLoS One, 2011, 6(9):e24080.
[60] Qi XS, Pajonk F, McCloskey S,et al. Radioresistance of the breast tumor is highly correlated to its level of cancer stem cell and its clinical implication for breast irradiation [J]. Radiother Oncol, 2017, 124(3):455-461.
[61] Pondé N, Brand?o M, El-Hachem G, et al. Treatment of advanced HER-2-positive breast cancer: 2018 and beyond [J]. Cancer Treat Rev, 2018, 67:10-20.
[62] Visus C, Ito D, Amoscato A, et al. Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck [J]. Cancer Res, 2007, 67(21):10 538-10 545.
[63] 王梦川, 吴爱国. 肿瘤特异性CD8+T细胞在三阴性乳腺癌免疫治疗中的应用 [J/CD].中华乳腺病杂志(电子版), 2017, 11(5):292-295.
[64] Croker AK, Allan AL. Inhibition of aldehyde dehydrogenase (ALDH) activity reduces chemotherapy and radiation resistance of stem-like ALDHhiCD44+ human breast cancer cells [J]. Breast Cancer Res Treat, 2012, 133(1):75-87.
[2] 赵晶, 付丽. 乳腺癌的分子分型 [J/CD]. 中华乳腺病杂志(电子版),2009, 3 (2):195-203.
[3] Oei AL, Vriend LE, Krawczyk PM, et al. Targeting therapy-resistant cancer stem cells by hyperthermia [EB/OL]. [2018-02-10]. https://www.tandfonline.com/doi/full/10.1080/02656736.2017.1279757.
[4] Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest [J]. 2011, 121(10):3804-9.
[5] 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 [J]. Cell Stem Cell, 2007, 1(5):555-567.
[6] Shima H, Yamada A, Ishikawa T, et al. Are breast cancer stem cells the key to resolving clinical issues in breast cancer therapy?[J]. Gland Surg, 2017, 6(1):82-88.
[7] Porkka K, Blomqvist C, Rissanen P, et al. Salvage therapies in women who fail to respond to first-line treatment with fluorouracil, epirubicin, and cyclophosphamide for advanced breast cancer [J]. J Clin Oncol, 1994, 12(8):1639-1647.
[8] Hara T, Iwadate M, Tachibana K, et al. Metastasis of breast cancer cells to the bone, lung, and lymph nodes promotes resistance to ionizing radiation [J]. Strahlenther Onkol, 2017, 193(10):848-855.
[9] Dontu G, Abdallah WM, Foley JM, et al. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells [J]. Genes Dev, 2003, 17(10):1253-1270.
[10] Dou J, Pan M, Wen P, et al. Isolation and identification of cancer stem-like cells from murine melanoma cell lines[J]. Cell Mol Immunol, 2007, 4(6):467-472.
[11] Marsden CG, Wright MJ, Pochampally R, et al. Breast tumor-initiating cells isolated from patient core biopsies for study of hormone action[J]. Methods Mol Biol, 2009, 590:363-375.
[12] Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice [J]. Nature, 1994, 367(6464):645-648.
[13] Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells [J]. Proc Natl Acad Sci USA, 2003, 100(7):3983-3988.
[14] Kanwal R, Shukla S, Walker E, et al. Acquisition of tumorigenic potential and therapeutic resistance in CD133+ subpopulation of prostate cancer cells exhibiting stem-cell like characteristics [J]. Cancer Lett, 2018,430:25-33.
[15] Satar NA, Fakiruddin KS, Lim MN, et al. Novel triplepositive markers identified in human nonsmall cell lung cancer cell line with chemotherapy-resistant and putative cancer stem cell characteristics [J]. Oncol Rep, 2018, 40(2):669-681.
[16] Patel SA, Ndabahaliye A, Lim PK, et al. Challenges in the development of future treatments for breast cancer stem cells [J]. Breast Cancer (Dove Med Press), 2010, 2:1-11.
[17] Ricardo S, Vieira AF, Gerhard R, et al. Breast cancer stem cell markers CD44, CD24 and ALDH1:expression distribution within intrinsic molecular subtype [J]. J Clin Pathol, 2011,64(11):937-946.
[18] Honeth G, Bendahl PO, Ringnér M, et al. The CD44+/CD24- phenotype is enriched in basal-like breast tumors [J]. Breast Cancer Res, 2008, 10(3):R53.
[19] Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct “side population” of cells with high drug efflux capacity in human tumor cells [J]. Proc Natl Acad Sci USA, 2004, 101(39):14 228-14 233.
[20] Nakanishi T, Chumsri S, Khakpour N, et al. Side-population cells in luminal-type breast cancer have tumour initiating cell properties, and are regulated by HER-2 expression and signaling [J]. Br J Cancer, 2010, 102(5):815-826.
[21] Charafe-Jauffret E, Ginestier C, Iovino F, et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature [J].Cancer Res,2009,69(4):1302-1313.
[22] Wright MH, Calcagno AM, Salcido CD, et al. Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics [J]. Breast Cancer Res, 2008,10(1):R10.
[23] 肖锡岗, 房林. 乳腺肿瘤干细胞筛选方法和治疗抵抗研究进展 [J/CD].中华乳腺病杂志(电子版), 2010, 4(3):329-338.
[24] Sarkar P, Basu K, Sarkar P, et al. Correlations of aldehyde dehydrogenase-1 (ALDH1) expression with traditional prognostic parameters and different molecular subtypes of breast carcinoma [J]. Clujul Med, 2018,91(2):181-187.
[25] Mansour SF, Atwa MM. Clinicopathological significance of CD133 and ALDH1 cancer stem cell marker expression in invasive ductal breast carcinoma [J]. Asian Pac J Cancer Prev, 2015,16(17):7491-7496.
[26] Liu S, Cong Y, Wang D, et al. Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts[J]. Stem Cell Reports, 2013, 2(1):78-91.
[27] Hartwig FP, Nedel F, Collares T, et al. Oncogenic somatic events in tissue-specific stem cells: a role in cancer recurrence?[J]. Ageing Res Rev, 2014,13:100-106.
[28] Zhang M, Lee AV, Rosen JM. The cellular origin and evolution of breast cancer [J]. Cold Spring Harb Perspect Med, 2017, 7(3). pii: a027128.
[29] Kotiyal S, Bhattacharya S. Breast cancer stem cells, EMT and therapeutic targets [J]. Biochem Biophys Res Commun, 2014, 453(1):112-116.
[30] Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells [J]. Cell, 2008, 133(4):704-715.
[31] Lim E, Vaillant F, Wu D, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers [J]. Nat Med, 2009,15(8):907-913.
[32] Shackleton M, Vaillant F, Simpson KJ, et al.Generation of a functional mammary gland from a single stem cell [J]. Nature, 2006, 439(7072):84-88.
[33] Brooks MD, Wicha MS. Tumor twitter: cellular communication in the breast cancer stem cell niche [J]. Cancer Discov, 2015, 5(5):469-471.
[34] Korkaya H, Kim GI, Davis A, et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER-2+ breast cancer by expanding the cancer stem cell population [J]. Mol Cell, 2012, 47(4):570-584.
[35] Bhola NE, Balko JM, Dugger TC, et al. TGF-beta inhibition enhances chemotherapy action against triple negative breast cancer [J]. J Clin Invest, 2013, 123(3):1348-1358.
[36] Singh JK, Sim?es BM, Howell SJ, et al. Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells [J]. Breast Cancer Res, 2013, 15(4):210.
[37] Jang GB, Hong IS, Kim RJ, et al. Wnt/β-catenin small-molecule inhibitor CWP232228 preferentially inhibits the growth of breast cancer stem-like cells [J]. Cancer Res, 2015, 75(8):1691-1702.
[38] Baker A, Wyatt D, Bocchetta M, et al. Notch-1-PTEN-ERK1/2 signaling axis promotes HER-2+ breast cancer cell proliferation and stem cell survival [J]. Oncogene, 2018, 37(33):4489-4504.
[39] Harrison H, Farnie G, Howell SJ, et al. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor [J]. Cancer Res, 2010,70(2):709-718.
[40] Wang D, Xu J, Liu B, et al. IL6 blockade potentiates the anti-tumor effects of γ-secretase inhibitors in Notch3-expressing breast cancer [J]. Cell Death Differ, 2018, 25(2):330-339.
[41] Zhou M, Hou Y, Yang G, et al. LncRNA-Hh strengthen cancer stem cells generation in twist-positive breast cancer via activation of Hedgehog signaling pathway [J]. Stem Cells, 2016, 34(1):55-56.
[42] Ramaswamy B, Lu Y, Teng KY, et al. Hedgehog signaling is a novel therapeutic target in tamoxifen-resistant breast cancer aberrantly activated by PI3K/AKT pathway [J]. Cancer Res, 2012, 72(19):5048-5059.
[43] Al-Ejeh F, Smart CE, Morrison BJ, et al. Breast cancer stem cells: treatment resistance and therapeutic opportunities [J]. Carcinogenesis, 2011, 32(5):650-658.
[44] Morrison BJ, Schmidt CW, Lakhani SR, et al. Breast cancer stem cells: implications for therapy of breast cancer [J]. Breast Cancer Res, 2008, 10(4):210.
[45] Rycaj K, Tang DG. Cancer stem cells and radioresistance [J]. Int J Radiat Biol, 2014,90(8):615-621.
[46] Vasiliou V, Vasiliou K, Nebert DW. Human ATP-binding cassette (ABC) transporter family [J]. Hum Genomics, 2009, 3(3):281-290.
[47] Leonard GD, Fojo T, Bates SE. The role of ABC transporters in clinical practice [J]. Oncologist, 2003, 8(5):411-424.
[48] Ma I, Allan AL. The role of human aldehyde dehydrogenase in normal and cancer stem cells [J]. Stem Cell Rev, 2011, 7(2):292-306.
[49] Young SZ, Bordey A. GABA’s control of stem and cancer cell proliferation in adult neural and peripheral niches [J]. Physiology (Bethesda), 2009, 24: 171-185.
[50] Tanei T, Morimoto K, Shimazu K, et al. Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential paclitaxel and epirubicin-based chemotherapy for breast cancers [J]. Clin Cancer Res, 2009,15(12):4234-4241.
[51] Singh S, Brocker C, Koppaka V, et al. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress [J]. Free Radic Biol Med, 2013, 56: 89-101.
[52] Woodward WA, Chen MS, Behbod F, et al. WNT/β-catenin mediates radiation resistance of mouse mammary progenitor cells [J]. Proc Natl Acad Sci U S A, 2007, 104(2):618-623.
[53] Munzone E, Colleoni M. Optimal management of luminal breast cancer: how much endocrine therapy is long enough? [J]. Ther Adv Med Oncol, 2018, 10:1-11.
[54] Sansone P, Berishaj M, Rajasekhar VK, et al. Evolution of cancer stem-like cells in endocrine-resistant metastatic breast cancers is mediated by stromal microvesicles [J]. Cancer Res, 2017, 77(8):1927-1941.
[55] Sim?es BM, Piva M, Iriondo O, et al. Effects of estrogen on the proportion of stem cells in the breast [J]. Breast Cancer Res Treat, 2011, 129(1):23-35.
[56] Leung EY, Askarian-Amiri ME, Sarkar D, et al. Endocrine therapy of estrogen receptor-positive breast cancer cells: early differential effects on stem cell markers [J]. Front Oncol, 2017,7:184.
[57] Bozorgi A, Khazaei M, Khazaei MR. New findings on breast cancer stem cells:a review [J]. J Breast Cancer, 2015,18(4):303-312.
[58] Ginestier C, Liu S, Diebel ME, et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts [J]. J Clin Invest, 2010, 120(2):485-497.
[59] Yin H, Glass J. The phenotypic radiation resistance of CD44+/CD24(-or low) breast cancer cells is mediated through the enhanced activation of ATM signaling [J]. PLoS One, 2011, 6(9):e24080.
[60] Qi XS, Pajonk F, McCloskey S,et al. Radioresistance of the breast tumor is highly correlated to its level of cancer stem cell and its clinical implication for breast irradiation [J]. Radiother Oncol, 2017, 124(3):455-461.
[61] Pondé N, Brand?o M, El-Hachem G, et al. Treatment of advanced HER-2-positive breast cancer: 2018 and beyond [J]. Cancer Treat Rev, 2018, 67:10-20.
[62] Visus C, Ito D, Amoscato A, et al. Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck [J]. Cancer Res, 2007, 67(21):10 538-10 545.
[63] 王梦川, 吴爱国. 肿瘤特异性CD8+T细胞在三阴性乳腺癌免疫治疗中的应用 [J/CD].中华乳腺病杂志(电子版), 2017, 11(5):292-295.
[64] Croker AK, Allan AL. Inhibition of aldehyde dehydrogenase (ALDH) activity reduces chemotherapy and radiation resistance of stem-like ALDHhiCD44+ human breast cancer cells [J]. Breast Cancer Res Treat, 2012, 133(1):75-87.