Isolation and Characterization of Stem-like Cells from a Human Ovarian Cancer Cell Line

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2011 Dec 14

PMID 22160925

Citations 47

Authors

Lijuan Wang

Roman Mezencev

Nathan J Bowen

Lilya V Matyunina

John F McDonald

Affiliations

Soon will be listed here.

Abstract

Increasing evidence supports the existence of a subpopulation of cancer cells capable of self-renewal and differentiation into diverse cell lineages. These cancer stem-like or cancer-initiating cells (CICs) also demonstrate resistance to chemo- and radiotherapy and may function as a primary source of cancer recurrence. We report here on the isolation and in vitro propagation of multicellular ovarian cancer spheroids from a well-established ovarian cancer cell line (OVCAR-3). The spheroid-derived cells (SDCs) display self-renewal potential, the ability to produce differentiated progeny, and increased expression of genes previously associated with CICs. SDCs also demonstrate higher invasiveness, migration potential, and enhanced resistance to standard anticancer agents relative to parental OVCAR-3 cells. Furthermore, SDCs display up-regulation of genes associated with epithelial-to-mesenchymal transition (EMT), anticancer drug resistance and/or decreased susceptibility to apoptosis, as well as, down-regulation of genes typically associated with the epithelial cell phenotype and pro-apoptotic genes. Pathway and biological process enrichment analyses indicate significant differences between the SDCs and precursor OVCAR-3 cells in TGF-beta-dependent induction of EMT, regulation of lipid metabolism, NOTCH and Hedgehog signaling. Collectively, our results indicate that these SDCs will be a useful model for the study of ovarian CICs and for the development of novel CIC-targeted therapies.

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References

Al-Hajj M, Wicha M, Benito-Hernandez A, Morrison S, Clarke M . Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003; 100(7):3983-8. PMC: 153034. DOI: 10.1073/pnas.0530291100. View

Lim Y, Oh S, Cha Y, Kim S, Jin X, Kim H . Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas. Oral Oncol. 2010; 47(2):83-91. DOI: 10.1016/j.oraloncology.2010.11.011. View

Bu R, Uddin S, Bavi P, Hussain A, Al-Dayel F, Ghourab S . HGF/c-Met pathway has a prominent role in mediating antiapoptotic signals through AKT in epithelial ovarian carcinoma. Lab Invest. 2010; 91(1):124-37. DOI: 10.1038/labinvest.2010.136. View

Liu S, Ye X, Malik A . Pyrrolidine dithiocarbamate prevents I-kappaB degradation and reduces microvascular injury induced by lipopolysaccharide in multiple organs. Mol Pharmacol. 1999; 55(4):658-67. View

Landen Jr C, Goodman B, Katre A, Steg A, Nick A, Stone R . Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther. 2010; 9(12):3186-99. PMC: 3005138. DOI: 10.1158/1535-7163.MCT-10-0563. View

Willis S, Adams J . Life in the balance: how BH3-only proteins induce apoptosis. Curr Opin Cell Biol. 2005; 17(6):617-25. PMC: 2930980. DOI: 10.1016/j.ceb.2005.10.001. View

Bao S, Wu Q, McLendon R, Hao Y, Shi Q, Hjelmeland A . Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006; 444(7120):756-60. DOI: 10.1038/nature05236. View

Chai J, Modak C, Mouazzen W, Narvaez R, Pham J . Epithelial or mesenchymal: Where to draw the line?. Biosci Trends. 2010; 4(3):130-42. View

Agarwal R, Kaye S . Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 2003; 3(7):502-16. DOI: 10.1038/nrc1123. View

10.

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

11.

Su Y, Qiu Q, Zhang X, Jiang Z, Leng Q, Liu Z . Aldehyde dehydrogenase 1 A1-positive cell population is enriched in tumor-initiating cells and associated with progression of bladder cancer. Cancer Epidemiol Biomarkers Prev. 2010; 19(2):327-37. PMC: 3544173. DOI: 10.1158/1055-9965.EPI-09-0865. View

12.

Pollock C, Rodriguez O, Martin P, Albanese C, Li X, Kopelovich L . Induction of metastatic gastric cancer by peroxisome proliferator-activated receptorδ activation. PPAR Res. 2011; 2010:571783. PMC: 3026990. DOI: 10.1155/2010/571783. View

13.

Kruyt F, Schuringa J . Apoptosis and cancer stem cells: Implications for apoptosis targeted therapy. Biochem Pharmacol. 2010; 80(4):423-30. DOI: 10.1016/j.bcp.2010.04.010. View

14.

Bender Kim C, Jackson E, Woolfenden A, Lawrence S, Babar I, Vogel S . Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005; 121(6):823-35. DOI: 10.1016/j.cell.2005.03.032. View

15.

Pineault N, Helgason C, Lawrence H, Humphries R . Differential expression of Hox, Meis1, and Pbx1 genes in primitive cells throughout murine hematopoietic ontogeny. Exp Hematol. 2002; 30(1):49-57. DOI: 10.1016/s0301-472x(01)00757-3. View

16.

Gao Q, Geng L, Kvalheim G, Gaudernack G, Suo Z . Identification of cancer stem-like side population cells in ovarian cancer cell line OVCAR-3. Ultrastruct Pathol. 2009; 33(4):175-81. DOI: 10.1080/01913120903086072. View

17.

Dean M, Fojo T, Bates S . Tumour stem cells and drug resistance. Nat Rev Cancer. 2005; 5(4):275-84. DOI: 10.1038/nrc1590. View

18.

Veeck J, Noetzel E, Bektas N, Jost E, Hartmann A, Knuchel R . Promoter hypermethylation of the SFRP2 gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer. Mol Cancer. 2008; 7:83. PMC: 2613402. DOI: 10.1186/1476-4598-7-83. View

19.

Ma L, Lai D, Liu T, Cheng W, Guo L . Cancer stem-like cells can be isolated with drug selection in human ovarian cancer cell line SKOV3. Acta Biochim Biophys Sin (Shanghai). 2010; 42(9):593-602. DOI: 10.1093/abbs/gmq067. View

20.

Ricci-Vitiani L, Lombardi D, Pilozzi E, Biffoni M, Todaro M, Peschle C . Identification and expansion of human colon-cancer-initiating cells. Nature. 2006; 445(7123):111-5. DOI: 10.1038/nature05384. View