肿瘤干细胞与化疗耐药

doi:10.3969/j.issn.1005-4979.2014.04.001

摘要/Abstract

摘要： 化疗是晚期肿瘤患者综合序列治疗的重要组成部分，但肿瘤细胞的耐药性常导致临床化疗失败。肿瘤干细胞能驱动肿瘤生成，如果化疗药物不能有效靶向作用于肿瘤干细胞，即使肿瘤缩小，残存的肿瘤干细胞也会迅速驱动肿瘤的复发。本文主要总结近年来关于肿瘤干细胞参与化疗耐药可能分子机制的研究成果，和靶向使肿瘤干细胞对治疗敏感性增加的新方法。

关键词: 肿瘤干细胞, 耐药, 化疗

Abstract: Chemotherapy is an indispensable component of systemic therapy on patients with advanced malignancies, yet the outcome is not always success due to the drug resistance of cancer cells. Cancer stem cells are a subpopulation of tumor cells that can initiate tumor formation. If chemotherapy kills bulk of cells within a tumor but not cancer stem cells, the surviving cancer stem cells can initiate the formation of recurrent tumors. This article discusses recent progresses related to cancer stem cell and drug resistance. Approaches to target cancer stem cells to improve the efficacy of chemotherapy will also be discussed.

Key words: cancer stem cell, drug resistance, chemotherapymolar, complication

中图分类号:

R789.8
R453

张萍. 肿瘤干细胞与化疗耐药[J]. 《口腔颌面外科杂志》, 2014, 24(4): 249-.

ZHANG Ping. Cancer Stem Cell and Drug Resistance[J]. 《Journal of Oral and Maxillofacial Surgery》, 2014, 24(4): 249-.

https://journal06.magtech.org.cn/Jweb_joms/CN/Y2014/V24/I4/249

参考文献

[1] Okamoto A, Chikamatsu K, Sakakura K, et al. Expansion and characterization of cancer stem-like cells in squamous cell carcinoma of the head and neck[J]. Oral Oncol, 2009,45(7):633-639.

[2] Chen YC, Chen YW, Hsu HS, et al. Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer[J]. Biochem Biophys Res Commun, 2009,385(3):307-313.

[3] Lee MH, Cho YS, Han YM. Simvastatin suppresses self-renewal of mouse embryonic stem cells by inhibiting RhoA geranylgeranylation[J]. Stem Cells, 2007,25(7):1654-1663.

[4] An Y, Kiang A, Lopez JP, et al. Cigarette smoke promotes drug resistance and expansion of cancer stem cell-like side population[J]. PLoS One, 2012,7(11):e47919.

[5] Staller P, Sulitkova J, Lisztwan J, et al. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL[J]. Nature, 2003,425(6955):307-311.

[6] Nakai E, Park K, Yawata T, et al. Enhanced MDR1 expression and chemoresistance of cancer stem cells derived from glioblastoma[J]. Cancer Invest, 2009,27(9):901-908.

[7] Zhang P, Zhang Y, Mao L, et al. Side population in oral squamous cell carcinoma possesses tumor stem cell phenotypes[J]. Cancer Lett, 2009,277(2):227-234.

[8] Chua C, Zaiden N, Chong KH, et al. Characterization of a side population of astrocytoma cells in response to temozolomide[J]. J Neurosurg, 2008,109(5):856-866.

[9] La Porta CA. Drug resistance in melanoma: new perspectives[J]. Curr Med Chem, 2007,14(4):387-391.

[10] Honoki K, Fujii H, Kubo A, et al. Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance[J]. Oncol Rep, 2010,24(2):501-505.

[11] Wang YC, Yo YT, Lee HY, et al. ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome[J]. Am J Pathol, 2012,180(3):1159-1169.

[12] 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.

[13] 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.

[14] Cheng L, Wu Q, Huang Z, et al. L1CAM regulates DNA damage checkpoint response of glioblastoma stem cells through NBS1[J]. EMBO J, 2011,30(5):800-813.

[15] Okuyama R, Nguyen BC, Talora C, et al. High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism[J]. Dev Cell, 2004,6(4):551-562.

[16] Nicolas M, Wolfer A, Raj K, et al. Notch1 functions as a tumor suppressor in mouse skin[J]. Nat Genet, 2003,33(3):416-421.

[17] Hu YY, Zheng MH, Cheng G, et al. Notch signaling contributes to the maintenance of both normal neural stem cells and patient-derived glioma stem cells[J]. BMC Cancer, 2011,11:82.

[18] Clement V, Sanchez P, de Tribolet N, et al. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity[J]. Curr Biol, 2007,17(2):165-172.

[19] Ehtesham M, Sarangi A, Valadez JG, et al. Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells[J]. Oncogene, 2007,26(39):5752-5761.

[20] Cui D, Xu Q, Wang K, et al. Gli1 is a potential target for alleviating multidrug resistance of gliomas[J]. J Neurol Sci, 2010,288(1-2):156-166.

[21] Bar EE, Chaudhry A, Lin A, et al. Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma[J]. Stem Cells, 2007,25(10):2524-2533.

[22] Mazzoleni S, Politi LS, Pala M, et al. Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis[J]. Cancer Res, 2010,70(19):7500-7513.

[23] Inda MM, Bonavia R, Mukasa A, et al. Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastoma[J]. Genes Dev, 2010,24(16):1731-1745.

[24] Mueller MM, Fusenig NE. Friends or foes - bipolar effects of the tumour stroma in cancer[J]. Nat Rev Cancer, 2004,4(11):839-849.

[25] Madjd Z, Mehrjerdi AZ, Sharifi AM, et al. CD44+ cancer cells express higher levels of the anti-apoptotic protein Bcl-2 in breast tumours[J]. Cancer Immun, 2009,9:4.

[26] Eisele L, Klein-Hitpass L, Chatzimanolis N, et al. Differential expression of drug-resistance-related genes between sensitive and resistant blasts in acute myeloid leukemia[J]. Acta Haematol, 2007,117(1):8-15.

[27] Ma S, Lee TK, Zheng BJ, et al. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway[J]. Oncogene, 2008,27(12):1749-1758.

[28] Wang SJ, Bourguignon LY. Hyaluronan and the interaction between CD44 and epidermal growth factor receptor in oncogenic signaling and chemotherapy resistance in head and neck cancer[J]. Arch Otolaryngol Head Neck Surg, 2006,132(7):771-778.

[29] Meads MB, Hazlehurst LA, Dalton WS. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance[J]. Clin Cancer Res, 2008,14(9):2519-2526.

[30] Akiyama K, Ohga N, Hida Y, et al. Tumor endothelial cells acquire drug resistance by MDR1 up-regulation via VEGF signaling in tumor microenvironment[J]. Am J Pathol, 2012,180(3):1283-1293.

[31] Boyer LA, Lee TI, Cole MF, et al. Core transcriptional regulatory circuitry in human embryonic stem cells[J]. Cell, 2005,122(6):947-956.

[32] Ye F, Zhou C, Cheng Q, et al. Stem-cell-abundant proteins Nanog, Nucleostemin and Musashi1 are highly expressed in malignant cervical epithelial cells[J]. BMC Cancer, 2008,8:108.

[33] Hoei-Hansen CE, Almstrup K, Nielsen JE, et al. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours[J]. Histopathology, 2005,47(1):48-56.

[34] Chiou SH, Yu CC, Huang CY, et al. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma[J]. Clin Cancer Res, 2008,14(13):4085-4095.

[35] Ezeh UI, Turek PJ, Reijo RA, et al. Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma[J]. Cancer, 2005,104(10):2255-2265.

[36] Jeter CR, Badeaux M, Choy G, et al. Functional evidence that the self-renewal gene NANOG regulates human tumor development[J]. Stem Cells, 2009,27(5):993-1005.

[37] Kumar SM, Liu S, Lu H, Zhang H, Zhang PJ, Gimotty PA, et al. Acquired cancer stem cell phenotypes through Oct4-mediated dedifferentiation[J]. Oncogene, 2012,31(47):4898-4911.

[38] Bourguignon LY, Wong G, Earle C, et al. Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma[J]. J Biol Chem, 2012,287(39):32800-32824.

[39] Hovinga KE, Shimizu F, Wang R, et al. Inhibition of notch signaling in glioblastoma targets cancer stem cells via an endothelial cell intermediate[J]. Stem Cells, 2010, 28(6):1019-1029.

[40] Bartel DP. MicroRNAs: target recognition and regulatory functions[J]. Cell, 2009,136(2):215-233.

[41] Lavon I, Zrihan D, Granit A, et al. Gliomas display amicroRNA expression profile reminiscent of neural precursor cells[J]. Neuro Oncol, 2010,12(5):422-433.

[42] Xu CX, Xu M, Tan L, et al. MicroRNA miR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog[J]. J Biol Chem, 2012,287(42):34970-34978.

[43] Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm[J]. Nat Rev Cancer, 2009,9(3):153-166.

[44] Han YK, Lee JH, Park GY, et al. A possible usage of a CDK4 inhibitor for breast cancer stem cell-targeted therapy[J]. Biochem Biophys Res Commun, 2013,430(4):1329-1333.

[45] Zhou J, Zhang Y. Cancer stem cells: Models, mechanisms and implications for improved treatment[J]. Cell Cycle, 2008,7(10):1360-1370.

[46] Ito K, Bernardi R, Morotti A, et al. PML targeting eradicates quiescent leukaemia-initiating cells[J]. Nature, 2008,453(7198):1072-1078.

选择文件类型/文献管理软件名称

选择包含的内容