Emerging role of cancer stem cells in the biology and treatment of ovarian cancer: basic knowledge and therapeutic possibilities for an innovative approach

Journal of Experimental & Clinical Cancer Research

Silverio Tomao²  Giuseppe Lo Russo²  Patrizia Vici³  Martina Strudel²  Luigi Rossi²  Anselmo Papa²  Federica Tomao¹ 

[1] Department of Gynaecology and Obstetrics, University of Rome “Sapienza”, Rome, Italy;Department of Medico-Surgical Sciences and Biotechnologies, University of Rome “Sapienza”, Latina, Italy;Department of Medical Oncology, National Cancer Institute of Rome, Rome, Italy

关键词: Target therapy;    Chemoresistance;    Ovarian cancer stem cells;    Epithelial ovarian cancer;   

Others  :  824835
DOI  :  10.1186/1756-9966-32-48

 received in 2013-06-26, accepted in 2013-07-29,  发布年份 2013

【 摘 要 】

In 2013 there will be an estimated 22,240 new diagnoses and 14,030 deaths from ovarian cancer in the United States. Despite the improved surgical approach and the novel active drugs that are available today in clinical practice, about 80% of women presenting with late-stage disease have a 5-year survival rate of only 30%. In the last years a growing scientific knowledge about the molecular pathways involved in ovarian carcinogenesis has led to the discovery and evaluation of several novel molecular targeted agents, with the aim to test alternative models of treatment in order to overcome the clinical problem of resistance. Cancer stem cells tend to be more resistant to chemotherapeutic agents and radiation than more differentiated cellular subtypes from the same tissue. In this context the study of ovarian cancer stem cells is taking on an increasingly important strategic role, mostly for the potential therapeutic application in the next future. In our review, we focused our attention on the molecular characteristics of epithelial ovarian cancer stem cells, in particular on possible targets to hit with targeted therapies.

【 授权许可】

   
2013 Tomao et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Murdoch WJ, McDonnel AC: Roles of the ovarian surface epithelium in ovulation and carcinogenesis. Reproduction 2002, 123(6):743-750.
• [2]Godwin AK, Testa JR, Hamilton TC: The biology of ovarian cancer development. Cancer 1993, 71(2 Suppl):530-536.
• [3]Ness RB, Cottreau C: Possible role of ovarian epithelial inflammation in ovarian cancer. J Natl Cancer Inst 1999, 91(17):1459-1467.
• [4]Siegel R, Ward E, Brawley O, Jemal A: Cancer statistics, 2011. CA Cancer J Clin 2011, 61:212-236.
• [5]Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin 2009, 59:225-249.
• [6]Boring CC, Squires TS, Tong T: Cancer statistics, 1993. CA Cancer J Clin 1993, 43:7-26.
• [7]Kusumbe AP, Bapat SA: Ovarian stem cell biology and the emergence of ovarian cancer stem cells. In Cancer Stem Cells. Edited by Bapat S, Hoboken NJ. Hoboken: John Wiley & Sons Inc; 2008:95-110.
• [8]Bast RC Jr, Hennessy B, Mills GB: The biology of ovarian cancer: new opportunities for translation. Nature Reviews. Cancer 2009, 9:415-428.
• [9]Wikborn C, Pettersson F, Silfversward C, Moberg PJ: Symptoms and diagnostic difficulties in ovarian epithelial cancer. Int J Gynaecol Obstet 1993, 42:261-264.
• [10]Ghasemi R, Grassadonia A, Tinari N, Piccolo E, Natoli C, Tomao F, Iacobelli S: Tumor-derived microvesicles: the metastasomes. Medical Hypotheses. Med Hypotheses 2013, 80(1):75-82.
• [11]Fleming GF, Ronnet BM, Seidman J: Epithelial ovarian cancer. In Principles and Practice of Gynecologic Oncology. 5th edition. Edited by Barakat RR, Markman M, Randal ME. Philadelphia: Lippincot Williams & Wilkins; 2009:763-836.
• [12]Kurman RJ, Shih Ie M: The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 2010, 34:433-443.
• [13]Kauffman RP, Griffin SJ, Lund JD, Tullar PE: Recommendations for cervical cancer screening: do they render the annual pelvic examination obsolete? Med Princ Practin press
• [14]Banerjee S, Kaye SB: New strategies in the treatment of ovarian cancer -current clinical perspectives and future potential. Clin Cancer Resin press
• [15]Hennessy BT, Coleman RL, Markman M: Ovarian cancer. Lancet 2009, 374:1371-82.
• [16]Ozols RF: Update on the management of ovarian cancer. Cancer J 2002, 8(Suppl 3):22-30.
• [17]Dalerba P, Cho RW, Clarke MF: Cancer stem cells: models and concepts. Annu Rev Med 2007, 58:267-284.
• [18]Jordan CT, Guzman ML, Noble M: Cancer stem cells. N Engl J Med 2006, 355:1253-1261.
• [19]Reya T, Morrison SJ, Clarke MF, Weissman IL: Stem cells, cancer, and cancer stem cells. Nature 2001, 414:105-111.
• [20]Alvero AB, Chen R, Fu HH, Montagna M, Schwartz PE, Rutherford T, Silasi DA, Steffensen KD, Waldstrom M, Visintin I, Mor G: Molecular phenotyping of human ovarian cancer stem cells unravel the mechanisms for repair and chemo-resistance. Cell Cycle 2009, 8(Suppl. 1):158-166.
• [21]Mor G, Yin G, Chefetz I, Yang Y, Alvero A: Ovarian cancer stem cells and inflammation. Cancer Biol Ther 2011, 11:708-713.
• [22]Bapat SA, Mali AM, Koppikar CB, Kurrey NK: Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 2005, 65:3025-3029.
• [23]Lim D, Oliva E: Precursors and pathogenesis of ovarian carcinoma. Pathology 2013, 45(3):229-42.
• [24]Auersperg N: The origin of ovarian carcinomas: a unifying hypothesis. Int J Gynecol Pathol 2011, 30(1):12-21.
• [25]Tinelli A, Vergara D, Martignago R, Leo G, Pisanò M, Malvasi A: An outlook on ovarian cancer and borderline ovarian tumors: focus on genomic and proteomic findings. Curr Genomics 2009, 10(4):240-9.
• [26]Farley J, Ozbun LL, Birrer MJ: Genomic analysis of epithelial ovarian cancer. Cell Res 2008, 18(5):538-48.
• [27]Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, Scurry JP, Scolyer RA, Smith AN, Bali A, Vanden Bergh P, Baron-Hay S, Scott C, Fink D, Hacker NF, Sutherland RL, O’Brien PM: A distinct molecular profile associated with mucinous epithelial ovarian cancer. Br J Cancer 2006, 94(6):904-13.
• [28]Kurrey NK, Amit K, Bapat SA: Snail and slug are major determinants of ovarian cancer invasiveness at the transcription level. Gynecol Oncol 2005, 97:155-165.
• [29]Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP: Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 2008, 68:4311-4320.
• [30]Deng S, Yang X, Lassus H, Liang S, Kaur S, Ye Q, Li C, Wang LP, Roby KF, Orsulic S, Connolly DC, Zhang Y, Montone K, Bützow R, Coukos G, Zhang L: Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform1 (ALDH1), in human epithelial cancers. PLoS ONE 2010, 5:e10277.
• [31]Silva IA, Bai S, McLean K, Yang K, Griffith K, Thomas D, Ginestier C, Johnston C, Kueck A, Reynolds RK, Wicha MS, Buckanovich RJ: Aldehyde dehydrogenase and CD133 define angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res 2011, 71:3991-4001.
• [32]Dyall S, Gayther SA, Dafou D: Cancer stem cells and epithelial ovarian cancer. Oncology: Journal of; 2010:105269.
• [33]Bast RC Jr, Mills GB: Personalizing therapy for ovarian cancer: BRCAness and beyond. J Clin Oncol 2010, 28(22):3545-3548.
• [34]Pardal R, Clarke MF, Morrison SJ: Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003, 3:895-902.
• [35]Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM: Cancer stem cells–perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 2006, 66:9339-9344.
• [36]Kurman RJ, Visvanathan K, Roden R, Wu TC, Shih IM: Early detection and treatment of ovarian cancer: shifting from early stage to minimal volume of disease based on a new model of carcinogenesis. Am J Obstet Gynecol 2008, 198:351-356.
• [37]Pisano C, Bruni GS, Facchini G, Marchetti C, Pignata S: Treatment of recurrent epithelial ovarian cancer. Ther Clin Risk Manag 2009, 5:421-426.
• [38]Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A: Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol 2010, 28:3323-3329.
• [39]Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Park YC, Parekh TV, Poveda AM: Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol 2010, 28:3107-3114.
• [40]Benedetti-Panici P, Perniola G, Marchetti C, Pernice M, Donfrancesco C, Di Donato V, Tomao F, Palaia I, Graziano M, Basile S, Bellati F: Intraperitoneal chemotherapy by ultrasound-guided direct puncture in recurrent ovarian cancer: feasibility, compliance, and complications. Int J Gynecol Cancer 2012, 22(6):1069-74.
• [41]Tomao F, Panici PB, Frati L, Tomao S: Emerging role of pemetrexed in ovarian cancer. Expert Rev Anticancer Ther 2009, 9(12):1727-35.
• [42]Bellati F, Napoletano C, Gasparri ML, Ruscito I, Marchetti C, Pignata S, Tomao F, Benedetti Panici P, Nuti M: Current knowledge and open issues regarding bevacizumab in gynecological neoplasms. Crit Rev Oncol Hematol 2012, 83(1):35-46.
• [43]Tomao F, Benedetti Panici P, Tomao S: Improvement in progression free survival in oceans bevacizumab arm: a critical point of view. J Clin Oncol 2013, 31(1):166-7.
• [44]Guarneri V, Piacentini F, Barbieri E, Conte PF: Achievements and unmet needs in the management of advanced ovarian cancer. Gynecol Oncol 2010, 117(2):152-158.
• [45]Itamochi H: Targeted therapies in epithelial ovarian cancer: molecular mechanisms of action. World Journal of Biological Chemistry 2010, 1(7):209-220.
• [46]Croker AK, Allan AL: Cancer stem cells: implications for the progression and treatment of metastatic disease. J Cell Mol Med 2008, 12(2):374-390.
• [47]Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006, 444(7120):756-760.
• [48]Molofsky AV, Pardal R, Morrison SJ: Diverse mechanisms regulate stem cell self-renewal. Curr Opin Cell Biol 2004, 16:700-707.
• [49]Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, Suri P, Wicha MS: Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 2006, 66(12):6063-6071.
• [50]Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J, Clouthier SG, Wicha MS: Regulation of mammary stem/progenitor cells by PTEN/Akt/β-catenin signaling. PLoS Biol 2009, 7(6):e1000121.
• [51]Miki J, Furusato B, Li H, Gu Y, Takahashi H, Egawa S, Sesterhenn IA, McLeod DG, Srivastava S, Rhim JS: Identification of putative stem cell markers, CD133 and CXCR4, in hTERTimmortalized primary nonmalignant and malignant tumorderived human prostate epithelial cell lines and in prostate cancer specimens. Cancer Res 2007, 67(7):3153-3161.
• [52]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: Breast cancer cell lines contain functional cancer stem sells with metastatic capacity and a distinct molecular signature. Cancer Res 2009, 69(4):1302-1313.
• [53]Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS: In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 2003, 17(10):1253-1270.
• [54]Widschwendter M, Fiegl H, Egle D, Mueller-Holzner E, Spizzo G, Marth C, Weisenberger DJ, Campan M, Young J, Jacobs I, Laird PW: Epigenetic stem cell signature in cancer. Nat Genet 2007, 39(2):157-158.
• [55]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, 100:3983-3988.
• [56]Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB: Identification of human brain tumour initiating cells. Nature 2004, 432:396-40.
• [57]Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A: Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 2007, 64:7011-7021.
• [58]O’Brien CA, Pollett A, Gallinger S, Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007, 445:106-110.
• [59]Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature 2007, 445:111-115.
• [60]Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 2007, 104:973-978.
• [61]Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM: Identification of pancreatic cancer stem cells. Cancer Res 2007, 67:1030-1037.
• [62]Dick JE, Bhatia M, Gan O, Kapp U: Assay of human stem cells by repopulation of NOD/SCID mice. Stem Cells 1997, 15(Suppl. 1):199-207.
• [63]Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ: Efficient tumour formation by single human melanoma cells. Nature 2008, 456(7222):593-598.
• [64]Bonnet D, Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997, 3:730-737.
• [65]Dalerba P, Clarke MF: Cancer stem cells and tumor metastasis: first steps into uncharted territory. Cell Stem Cell 2007, 1:241-242.
• [66]Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF: Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 2007, 104:10158-10163.
• [67]Hill RP: Identifying cancer stem cells in solid tumors: case not proven. Cancer Res 2006, 66:1891-1895.
• [68]Hill RP, Perris R: “Destemming” cancer stem cells. J Natl Cancer Inst 2007, 99:1435-1440.
• [69]Vogel G: Stem cells. ‘Stemness’ genes still elusive. Science 2003, 302:371.
• [70]Orkin SH, Zon LI: Hematopoiesis: an evolving paradigm for stem cell biology. Cell 2008, 132:631-644.
• [71]McNiece I: The CD34 + Thy1+ cell population: are they all stem cells? Exp Hematol 2000, 28:1312-1314.
• [72]Zon LI: Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal. Nature 2008, 453:306-313.
• [73]Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW: AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997, 90:5002-5012.
• [74]Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE: Generation of a functional mammary gland from a single stem cell. Nature 2006, 439:84-88.
• [75]Spangrude GJ, Brooks DM: Mouse strain variability in the expression of the hematopoietic stem cell antigen Ly-6A/E by bone marrow cells. Blood 1993, 82:3327-3332.
• [76]Corbeil D, Röper K, Hellwig A, Tavian M, Miraglia S, Watt SM, Simmons PJ, Peault B, Buck DW, Huttner WB: The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 2000, 275(8):5512-5520.
• [77]Ferrandina G, Bonanno G, Pierelli L, Perillo A, Procoli A, Mariotti A, Corallo M, Martinelli E, Rutella S, Paglia A, Zannoni G, Mancuso S, Scambia G: Expression of CD133-1 and CD133-2 in ovarian cancer. Int J Gynecol Cancer 2008, 18:506-514.
• [78]Baba T, Convery PA, Matsumura N, Whitaker RS, Kondoh E, Perry T, Huang Z, Bentley RC, Mori S, Fujii S, Marks JR, Berchuck A, Murphy SK: Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene 2009, 28(2):209-218.
• [79]Curley MD, Therrien VA, Cummings CL, Sergent PA, Koulouris CR, Friel AM, Roberts DJ, Seiden MV, Scadden DT, Rueda BR, Foster R: CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells 2009, 27(12):2875-83.
• [80]Heider KH, Kuthan H, Stehle G, Munzert G: CD44v6: a target for antibody-based cancer therapy. Cancer Immunol Immunother 2004, 53:567-579.
• [81]Chen J, Wang J, Chen D, Yang J, Yang C, Zhang Y, Zhang H, Dou J: Evaluation of characteristics of CD44 + CD117+ ovarian cancer stem cells in three dimensional basement membrane extract scaffold versus two dimensional monocultures. BMC Cell Biol 2013, 14:7.
• [82]Wei X, Dombkowski D, Meirelles K, Pieretti-Vanmarcke R, Szotek PP, Chang HL, Preffer FI, Mueller PR, Teixeira J, MacLaughlin DT, Donahoe PK: Mullerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics. Proc Natl Acad Sci USA 2010, 107(44):18874-9.
• [83]Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC: Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 1996, 183:1797-1806.
• [84]Kvinlaug BT, Huntly BJ: Targeting cancer stem cells. Expert Opin Ther Targets 2007, 11:915-927.
• [85]Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A, Nakauchi H, Taniguchi H: Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 2006, 44:240-251.
• [86]Seigel GM, Campbell LM, Narayan M, Gonzalez-Fernandez F: Cancer stem cell characteristics in retinoblastoma. Mol Vis 2005, 11:729-737.
• [87]Haraguchi N, Utsunomiya T, Inoue H, Tanaka F, Mimori K, Barnard GF, Mori M: Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 2006, 24:506-513.
• [88]Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, Goodell MA, Brenner MK: A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci 2004, 101:14228-14233.
• [89]Kondo T, Setoguchi T, Taga T: Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci 2004, 101:781-786.
• [90]Wulf GG, Wang RY, Kuehnle I, Weidner D, Marini F, Brenner MK, Andreeff M, Goodell MA: A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood 2001, 98:1166-1173.
• [91]Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, Dombkowski D, Preffer F, MacLaughlin DT, Donahoe PK: Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci USA 2006, 103:11154-11159.
• [92]Moserle L, Indraccolo S, Ghisi M, Frasson C, Fortunato E, Canevari S, Miotti S, Tosello V, Zamarchi R, Corradin A, Minuzzo S, Rossi E, Basso G, Amadori A: The side population of ovarian cancer cells is a primary target of IFN-alpha antitumor effects. Cancer Res 2008, 68:5658-5668.
• [93]Kristiansen G, Sammar M, Altevogt P: Tumour biological aspects of CD24, a mucin-like adhesion molecule. J Mol Histol 2004, 35(3):255-262.
• [94]Gao MQ, Choi YP, Kang S, Youn JH, Cho NH: CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells. Oncogene 2010, 29(18):2672-2680.
• [95]Miettinen M, Lasota J: KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Applied Immunohistochemistry and Molecular Morphology 2005, 13(3):205-220.
• [96]Luo L, Zeng J, Liang B, Zhao Z, Sun L, Cao D, Yang J, Shen K: Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome. Exp Mol Pathol 2011, 91:596-602.
• [97]Raspollini MR, Amunni G, Villanucci A, Baroni G, Taddei A, Taddei GL: c-KIT expression and correlation with chemotherapy resistance in ovarian carcinoma: an immunocytochemical study. Ann Oncol 2004, 15(4):594-597. 2004
• [98]Chau WK, Ip CK, Mak AS, Lai HC, Wong AS: c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/beta-catenin-ATP-binding cassette G2 signaling. Oncogenein press
• [99]Imrich S, Hachmeister M, Gires O: EpCAM and its potential role in tumor-initiating cells. Cell Adh Migr 2012, 6:30-38.
• [100]Pauli C, Münz M, Kieu C, Mack B, Breinl P, Wollenberg B, Lang S, Zeidler R, Gires O: Tumor-specific glycosylation of the carcinoma-associated epithelial cell adhesion molecule EpCAM in head and neck carcinomas. Cancer Lett 2003, 193(1):25-32.
• [101]Gosens MJEM, Van Kempen LCL, Van De Velde CHJ, Van Krieken JHJM, Nagtegaal ID: Loss of membranous Ep-CAM in budding colorectal carcinoma cells. Mod Pathol 2007, 20(2):221-232.
• [102]Baeuerle PA, Gires O: EpCAM (CD326) finding its role in cancer. Br J Cancer 2007, 96(3):417-423.
• [103]Thiery JP, Acloque H, Huang RYJ, Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell 2009, 139(5):871-890.
• [104]Moreb JS: Aldehyde dehydrogenase as a marker for stem cells. Curr Stem Cell Res Ther 2008, 3:237-246.
• [105]Glinsky GV, Olga Berezovska O, Glinskii AB: Microarray analysis identifies a death from cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest 2005, 115:1503-1521.
• [106]Shi J, Zhou Z, Di W, Li N: Correlation of CD44v6 expression with ovarian cancer progression and recurrence. BMC Cancer 2013, 13:182.
• [107]Rosanò L, Cianfrocca R, Spinella F, Di Castro V, Nicotra MR, Lucidi A, Ferrandina G, Natali PG, Bagnato A: Acquisition of chemoresistance and EMT phenotype is linked with activation of the endothelin A receptor pathway in ovarian carcinoma cells. Clin Cancer Res 2011, 17(8):2350-60.
• [108]Tilly JL, Rueda BR: Minireview: stem cell contribution to ovarian development, function, and disease. Endocrinology 2008, 149:4307-4311.
• [109]Kobel M, Kalloger SE, Boyd N, McKinney S, Mehl E, Palmer C, Leung S, Bowen NJ, Ionescu DN, Rajput A, Prentice LM, Miller D, Santos J, Swenerton K, Gilks CB, Huntsman D: Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med 2008, 5(12):e232.
• [110]Lawrenson K, Gayther SA: Ovarian cancer: a clinical challenge that needs some basic answers. PLoS Med 2009, 6:e25.
• [111]Tothill IE: Biosensors for cancer markers diagnosis. Semin Cell Dev Biol 2009, 20:55-62.
• [112]Landen CN Jr, Goodman B, Katre AA, Steg AD, Nick AM, Stone RL, Miller LD, Mejia PV, Jennings NB, Gershenson DM, Bast RC Jr, Coleman RL, Lopez-Berestein G, Sood AK: Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther 2010, 9(12):3186-3199.
• [113]Wani AA, Sharma N, Shouche YS, Bapat SA: Nuclear-mitochondrial genomic profiling reveals a pattern of evolution in epithelial ovarian tumor stem cells. Oncogene 2006, 25:6336-6344.
• [114]Frosina G: DNA repair in normal and cancer stem cells, with special reference to the central nervous system. Curr Med Chem 2009, 16:854-866.
• [115]Lee AS, Kahatapitiya P, Kramer B, Joya JE, Hook J, Liu R, Schevzov G, Alexander IE, McCowage G, Montarras D, Gunning PW, Hardeman EC: Methylguanine DNA methyltransferase-mediated drug resistance-based selective enrichment and engraftment of transplanted stem cells in skeletal muscle. Stem Cells 2009, 27:1098-1108.
• [116]Clarke-Pearson DL: Clinical practice–screening for ovarian cancer. N Engl J Med 2009, 361:170-177.
• [117]Schwartz PE: Neoadjuvant chemotherapy for the management of ovarian cancer. Best Practice & Research. Clin Obstet Gynaecol 2002, 16:585-596.
• [118]Phillips TM, McBride WH, Pajonk F: The response of CD24(−/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst 2006, 98:1777-1785.
• [119]Blagosklonny MV: Cancer stem cell and cancer stemloids: from biology to therapy. Cancer Biol Ther 2007, 6:1684-1690.
• [120]Ishii H, Iwatsuki M, Ieta K, Ohta D, Haraguchi N, Mimori K, Mori M: Cancer stem cells and chemoradiation resistance. Cancer Sci 2008, 99:1871-1877.
• [121]Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
• [122]Gimenez-Bonafe P, Tortosa A, Perez-Tomas R: Overcoming drug resistance by enhancing apoptosis of tumor cells. Curr Cancer Drug Targets 2009, 9:320-340.
• [123]Dean M: ABC transporters, drug resistance, and cancer stem cells. J Mammary Gland Biol Neoplasia 2009, 14:3-9.
• [124]Szaka’cs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM: Targeting multidrug resistance in cancer. Nat Rev Drug Discov 2006, 5:219-234.
• [125]Donnenberg VS, Meyer EM, Donnenberg AD: Measurement of multiple drug resistance transporter activity in putative cancer stem/progenitor cells. Methods Mol Biol 2009, 568:261-279.
• [126]Guo Y, Kock K, Ritter CA, Chen ZS, Grube M, Jedlitschky G, Illmer T, Ayres M, Beck JF, Siegmund W, Ehninger G, Gandhi V, Kroemer HK, Kruh GD, Schaich M: Expression of ABCC-type nucleotide exporters in blasts of adult acute myeloid leukemia: relation to long-term survival. Clin Cancer Res 2009, 15:1762-1769.
• [127]Martin V, Xu J, Pabbisetty SK, Alonso MM, Liu D, Lee OH, Gumin J, Bhat KP, Colman H, Lang FF, Fueyo J, Gomez-Manzano C: Tie2-mediated multidrug resistance in malignant gliomas is associated with upregulation of ABC transporters. Oncogene 2009, 28:2358-2363.
• [128]van Herwaarden AE, Wagenaar E, Karnekamp B, Merino G, Jonker JW, Schinkel AH: Breast cancer resistance protein (Bcrp1/Abcg2) reduces systemic exposure of the dietary carcinogens aflatoxin B1, IQ and Trp-P-1 but also mediates their secretion into breast milk. Carcinogenesis 2006, 27:123-130.
• [129]Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP: The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 2001, 7:1028-1034.
• [130]Alvi AJ, Clayton H, Joshi C, Enver T, Ashworth A, Vivanco M, Dale TC, Smalley MJ: Functional and molecular characterisation of mammary side population cells. Breast Cancer Res 2003, 5:R1-R8.
• [131]Cervello I, Gil-Sanchis C, Mas A, Delgado-Rosas F, Martínez-Conejero JA, Galán A, Martínez-Romero A, Martínez S, Navarro I, Ferro J, Horcajadas JA, Esteban FJ, O’Connor JE, Pellicer A, Simón C: Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells. PLoS One 2010, 5:e10964.
• [132]Hosonuma S, Kobayashi Y, Kojo S, Wada H, Seino K, Kiguchi K, Ishizuka B: Clinical significance of side population in ovarian cancer cells. Hum Cell 2011, 24:9-12.
• [133]Hu L, McArthur C, Jaffe RB: Ovarian cancer stemlike side-population cells are tumourigenic and chemoresistant. Br J Cancer 2010, 102:1276-1283.
• [134]Grivennikov SI, Greten FR, Karin M: Immunity, inflammation, and cancer. Cell 2010, 140:883-899.
• [135]Kamazawa S, Kigawa J, Kanamori Y, Itamochi H, Sato S, Iba T, Terakawa N: Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer. Gynecol Oncol 2002, 86:171-176.
• [136]Rodriguez-Antona C: Pharmacogenomics of paclitaxel. Pharmacogenomics 2010, 11:621-623.
• [137]Anderson ME: Glutathione: an overview of biosynthesis and modulation. Chem Biol Interact 1998, 111–112:1-14.
• [138]Backos DS, Franklin CC, Reigan P: The role of glutathione in brain tumor drug resistance. Biochem Pharmacol 2012, 83(8):1005-1012.
• [139]Jedlitschky G, Leier I, Buchholz U, Center M, Keppler D: ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein. Cancer Res 1994, 54(18):4833-4836.
• [140]Wu WJ, Zhang Y, Zeng ZL, Li XB, Hu KS, Luo HY, Yang J, Huang P, Xu RH: β-phenylethyl isothiocyanate reverses platinum resistance by a GSH-dependent mechanism in cancer cells with epithelial-mesenchymal transition phenotype. Biochem Pharmacol 2013, 85(4):486-96.
• [141]Lessard J, Sauvageau G: Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 2003, 423(6937):255-260.
• [142]Liu J, Cao L, Chen J, Song S, Lee IH, Quijano C, Liu H, Keyvanfar K, Chen H, Cao LY, Ahn BH, Kumar NG, Rovira II, Xu XL, van Lohuizen M, Motoyama N, Deng CX, Finkel T: Bmi1 regulatesmitochondrial function and the DNA damage response pathway. Nature 2009, 459(7245):387-392.
• [143]Li J, Gong LY, Song LB, Jiang LL, Liu LP, Wu J, Yuan J, Cai JC, He M, Wang L, Zeng M, Cheng SY, Li M: Oncoprotein Bmi-1 renders apoptotic resistance to glioma cells through activation of the IKK-nuclear factor-kappaB-pathway. Am J Pathol 2010, 176(2):699-709.
• [144]Guo BH, Feng Y, Zhang R, Xu LH, Li MZ, Kung HF, Song LB, Zeng MS: Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer. Mol Cancer 2011, 10:10.
• [145]Wang E, Bhattacharyya S, Szabolcs A, Rodriguez-Aguayo C, Jennings NB, Lopez-Berestein G, Mukherjee P, Sood AK, Bhattacharya R: Enhancing chemotherapy response with Bmi-1 silencing in ovarian cancer. PLoS ONE 2011, 6(3):e17918.
• [146]Fraser M, Bai T, Tsang BK: Akt promotes cisplatin resistance in human ovarian cancer cells through inhibition of p53 phosphorylation and nuclear function. Int J Cancer 2008, 122(3):534-546.
• [147]Nikolaev AY, Li M, Puskas N, Qin J, Gu W: Parc: a cytoplasmic anchor for p53. Cell 2003, 112(1):29-40.
• [148]Woo MG, Xue K, Liu J, McBride H, Tsang BK: Calpain-mediated processing of p53-associated parkin-like cytoplasmic protein (PARC) affects chemosensitivity of human ovarian cancer cells by promoting p53 subcellular trafficking. J Biol Chem 2012, 287(6):3963-3975.
• [149]Wallace-Brodeur RR, Lowe SW: Clinical implications of p53 mutations. Cell Mol Life Sci 1999, 55:64-75.
• [150]Kusumbe AP, Bapat SA: Cancer stem cells and aneuploid populations within developing tumors are the major determinants of tumor dormancy. Cancer Res 2009, 69:9245-9253.
• [151]Peinado H, Portillo F, Cano A: Transcriptional regulation of cadherins during development and carcinogenesis. Int J Dev Biol 2004, 48:365-375.
• [152]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: The epithelialmesenchymal transition generates cells with properties of stem cells. Cell 2008, 133(4):704-715.
• [153]Peinado H, Olmeda D, Cano A: Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 2007, 7:415-428.
• [154]Zavadil J, Bitzer M, Liang D, Yang YC, Massimi A, Kneitz S, Piek E, Bottinger EP: Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. PNAS 2001, 98:6686-6691.
• [155]Polyak K, Weinberg RA: Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009, 9:265-273.
• [156]Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY, Bapat SA: Snail and Slug mediate radio- and chemo-resistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells 2009, 27:2059-2068.
• [157]Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES: Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 2009, 138:645-659.
• [158]Wicha MS, Liu S, Dontu G: Cancer stem cells: an old idea–a paradigm shift. Cancer Res 2006, 66:1883-1890.
• [159]Sell S, Pierce GB: Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab Invest 1994, 70:6-22.
• [160]Reed EC: Cisplatin. Cancer Chemother Biol Response Modif 1999, 18:144-151.
• [161]Rolitsky CD, Theil KS, McGaughy VR, Copeland LJ, Niemann TH: HER-2/neu amplification and overexpression in endometrial carcinoma. Int J Gynecol Pathol 1999, 18:138-143.
• [162]Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989, 244:707-712.
• [163]Kim JW, Lee CG, Lyu MS, Kim HK, Rha JG, Kim DH, Kim SJ, Namkoong SE: A new cell line from human undifferentiated carcinoma of the ovary: establishment and characterization. J Cancer Res Clin Oncol 1997, 123:82-90.
• [164]Perez-Caro M, Cobaleda C, Gonzalez-Herrero I, Vicente-Dueñas C, Bermejo-Rodríguez C, Sánchez-Beato M, Orfao A, Pintado B, Flores T, Sánchez-Martín M, Jiménez R, Piris MA, Sánchez-García I: Cancer induction by restriction of oncogene expression to the stem cell compartment. EMBO J 2009, 28:8-20.
• [165]Lara PC, Lloret M, Clavo B, Apolinario RM, Henríquez-Hernández LA, Bordón E, Fontes F, Rey A: Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression. Radiat Oncol 2009, 4:29.
• [166]Elloul S, Vaksman O, Stavnes HT, Trope CG, Davidson B, Reich R: Mesenchymal-to-epithelial transition determinants as characteristics of ovarian carcinoma effusions. Clin Exp Metastasis 2010, 27:161-172.
• [167]Pistollato F, Abbadi S, Rampazzo E, Persano L, Della Puppa A, Frasson C, Sarto E, Scienza R, D’avella D, Basso G: Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma. Stem Cells 2010, 28:851-862.
• [168]Greijer AE, van der Groep P, Kemming D, Shvarts A, Semenza GL, Meijer GA, van de Wiel MA, Belien JA, van Diest PJ, van der Wall E: Upregulation of gene expression by hypoxia is mediated predominantly by hypoxia-inducible factor 1 (HIF-1). J Pathol 2005, 206(3):291-304.
• [169]Levine AJ, Puzio-Kuter AM: The control of themetabolic switch in cancers by oncogenes and tumor suppressor genes. Science 2010, 3(330(6009)):1340-4.
• [170]DeBerardinis RJ: Is cancer a disease of abnormal cellular metabolism? New angles on an old idea. Genet Med 2008, 10:767-777.
• [171]Smith LM, Nesterova A, Ryan MC, Duniho S, Jonas M, Anderson M, Zabinski RF, Sutherland MK, Gerber HP, Van Orden KL, Moore PA, Ruben SM, Carter PJ: CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br J Cancer 2008, 99:100-109.
• [172]Orian-Rousseau V: CD44, a therapeutic target for metastasizing tumours. Eur J Cancer 2010, 46:1271-7.
• [173]De Stefano I, Battaglia A, Zannoni GF, Prisco MG, Fattorossi A, Travaglia D, Baroni S, Renier D, Scambia G, Ferlini C, Gallo D: Hyaluronic acid-paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts. Cancer Chemother Pharmacol 2011, 68(1):107-16.
• [174]Bretz NP, Salnikov AV, Perne C, Keller S, Wang X, Mierke CT, Fogel M, Erbe-Hofmann N, Schlange T, Moldenhauer G, Altevogt P: CD24 controls Src/STAT3 activity in human tumors. Cell Mol Life Sci 2012, 69(22):3863-3879.
• [175]Su D, Deng H, Zhao X, Zhang X, Chen L, Chen X, Li Z, Bai Y, Wang Y, Zhong Q, Yi T, Qian Z, Wei Y: Targeting CD24 for treatment of ovarian cancer by short hairpin RNA. Cytotherapy 2009, 11(5):642-652.
• [176]Schilder RJ, Sill MW, Lee RB, Shaw TJ, Senterman MK, Klein-Szanto AJ, Miner Z, Vanderhyden BC: Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a gynecologic oncology group study. J Clin Oncol 2008, 26(20):3418-3425.
• [177]Patel BB, He YA, Li XM, Frolov A, Vanderveer L, Slater C, Schilder RJ, von Mehren M, Godwin AK, Yeung AT: Molecular mechanisms of action of imatinib mesylate in human ovarian cancer: a proteomic analysis. Cancer Genomics Proteomics 2008, 5:137-150.
• [178]Sebastian M, Kuemmel A, Schmidt M, Schmittel A: Catumaxomab: a bispecific trifunctional antibody. Drugs of Today 2009, 45(8):589-597.
• [179]Seimetz D, Lindhofer H, Bokemeyer C: Development and approval of the trifunctional antibody catumaxomab (anti- EpCAM × anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev 2010, 36(6):458-467.
• [180]Marchitti SA, Brocker C, Stagos D, Vasiliou V: Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin Drug Metab Toxicol 2008, 4(6):697-720.
• [181]Liu P, Brown S, Goktug T, Channathodiyil P, Kannappan V, Hugnot JP, Guichet PO, Bian X, Armesilla AL, Darling JL, Wang W: Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH positive cancer-stem-like cells. Br J Cancer 2010, 107(9):1488-1497.
• [182]Soignet SL, Benedetti F, Fleischauer A, Parker BA, Truglia JA, Ra Crisp M, Warrell RP Jr: Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia. Leukemia 1998, 12(10):1518-1521.
• [183]Sell S: Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 2004, 51(1):1-28.
• [184]Lim YC, Kang HJ, Kim YS, Choi EC: All-trans-retinoic acid inhibits growth of head and neck cancer stem cells by suppression ofWnt/beta-catenin pathway. Eur J Cancer 2012, 48(17):3310-3318.
• [185]Whitworth JM, Londoño-Joshi AI, Sellers JC, Oliver PJ, Muccio DD, Atigadda VR, Straughn JM Jr, Buchsbaum DJ: The impact of novel retinoids in combination with platinum chemotherapy on ovarian cancer stem cells. Gynecol Oncol 2012, 125(1):226-230.
• [186]Ruiz-Vela A, Aguilar-Gallardo C, Martínez-Arroyo AM, Soriano-Navarro M, Ruiz V, Simón C: Specific unsaturated fatty acids enforce the transdifferentiation of human cancer cells toward adipocyte-like cells. Stem Cell Rev 2011, 7(4):898-909.
• [187]Yin G, Alvero AB, Craveiro V, Holmberg JC, Fu HH, Montagna MK, Yang Y, Chefetz-Menaker I, Nuti S, Rossi M, Silasi DA, Rutherford T, Mor G: Constitutive proteasomal degradation of TWIST-1 in epithelial-ovarian cancer stem cells impacts differentiation and metastatic potential. Oncogene 2013, 32:39-49.
• [188]Jain AK, Allton K, Iacovino M, Mahen E, Milczarek RJ, Zwaka TP, Kyba M, Barton MC: p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells. PLoS Biol 2012, 10(2):1001268.
• [189]Yu Z, Li Y, Fan H, Liu Z, Pestell RG: miRNAs regulate stem cell self-renewal and differentiation. Frontiers in Genetics 2012, 3:191-195.
• [190]Davis ME, Chen ZG, Shin DM: Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 2008, 7(9):771-782.
• [191]Chen ZG: Small-molecule delivery by nanoparticles for anticancer therapy. Trends Mol Med 2010, 16(12):594-602.
• [192]Ruiz-Vela A, Aguilar-Gallardo C, Simón C: Building a framework for embryonic microenvironments and cancer stem cells. Stem Cell Reviews and Reports 2010, 5(4):319-327.
• [193]Li HJ, Reinhardt F, Herschman HR, Weinberg RA: Cancer stimulated mesenchymal stemcells create a carcinoma stem cell niche via prostaglandin E2 signaling. Cancer Discovery 2012, 2:840-855.
• [194]Lis R, Touboul C, Raynaud CM, Malek JA, Suhre K, Mirshahi M, Rafii A: Mesenchymal cell interaction with ovarian cancer cells triggers pro-metastatic properties. PLoS One 2012, 7(5):38340.
• [195]Katz E, Skorecki K, Tzukerman M: Niche-dependent tumorigenic capacity of malignant ovarian ascites-derived cancer ceil subpopulations. Clin Cancer Res 2009, 15(1):70-80.
• [196]Liang D, Ma Y, Liu J, Trope CG, Holm R, Nesland JM, Suo Z: The hypoxic microenvironment upgrades stem-like properties of ovarian cancer cells. BMC Cancer 2012, 12:201-211.
• [197]La Barge MA: The difficulty of targeting cancer stem cell niches. Clin Cancer Res 2010, 16(12):3121-3129.
• [198]Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell 2009, 136(2):215-233.
• [199]Lavon I, Zrihan D, Granit A, Einstein O, Fainstein N, Cohen MA, Cohen MA, Zelikovitch B, Shoshan Y, Spektor S, Reubinoff BE, Felig Y, Gerlitz O, Ben-Hur T, Smith Y, Siegal T: Gliomas display a microRNA expression profile reminiscent of neural precursor cells. Neuro Oncol 2010, 12(5):422-433.
• [200]van Jaarsveld MTM, Helleman J, Berns EMJJ, Wiemer EAC: MicroRNAs in ovarian cancer biology and therapy resistance. Int J Biochem Cell Biol 2010, 42(8):1282-1290.
• [201]Xu CX, Xu M, Tan L, Yang H, Permuth-Wey J, Kruk PA, Wenham RM, Nicosia SV, Lancaster JM, Sellers TA, Cheng JQ: MicroRNA MiR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog. J Biol Chem 2012, 287(42):34970-34978.
• [202]Cheng W, Liu T, Wan X, Gao Y, Wang H: MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J 2012, 279(11):2047-2059.
• [203]Wu Q, Guo R, Lin M, Zhou B, Wang Y: MicroRNA- 200a inhibits CD133/1+ ovarian cancer stem cells migration and invasion by targeting E-cadherin repressor ZEB2. Gynecol Oncol 2011, 122(1):149-154.
• [204]Sarkar FH, Li Y, Wang Z, Kong D, Ali S: Implication of microRNAs in drug resistance for designing novel cancer therapy. Drug Resist Updat 2010, 13(3):57-66.
• [205]Zhong X, Li N, Liang S, Huang Q, Coukos G, Zhang L: Identification of microRNAs regulating reprogramming factor LIN28 in embryonic stem cells and cancer cells. J Biol Chem 2010, 285(53):41961-41971.
• [206]Djordjevic B, Stojanovic S, Conic I, Jankovic-Velickovic L, Vukomanovic P, Zivadinovic R, Vukadinovic M: Current approach to epithelial ovarian cancer based on the concept of cancer stem cells. J BUON 2012, 17(4):627-36.
• [207]Chefetz I, Alvero AB, Holmberg JC, Lebowitz N, Craveiro V, Yang-Hartwich Y, Yin G, Squillace L, Gurrea Soteras M, Aldo P, Mor G: TLR2 enhances ovarian cancer stem cell self-renewal and promotes tumor repair and recurrence. Cell Cycle 2013, 12(3):511-21.
• [208]Kang KS, Choi YP, Gao MQ, Kang S, Kim BG, Lee JH, Kwon MJ, Shin YK, Cho NH: CD24(+) ovary cancer cells exhibit an invasive mesenchymal phenotype. Biochem Biophys Res Commun 2013, 432(2):333-8.