Abstract
Ovarian cancer is a complex disease, with unclear origins, complicated, multistep tumorigenesis, and variable outcomes. As such, generating experimental models to study the disease and treatment efficacies has proven to be extremely challenging. A number of studies have utilized monolayer in vitro experiments to decipher the cellular changes in ovarian cancer and responses to different treatment approaches. Others have generated three-dimensional spheroid cultures to evaluate cellular function in an environment with more physiological contact with other cells and their matrices. Lastly, a variety of in vivo models have been used to investigate the onset and progression of ovarian cancer and how tumors respond to treatments in an intact physiological environment. This chapter discusses a number of different experimental approaches to study the etiology, biology, and pathology of ovarian tumors and their response to different anticancer therapies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29
Tan DS, Agarwal R, Kaye SB (2006) Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol 7:925–934
Shepherd TG, Theriault BL, Campbell EJ, Nachtigal EW (2006) Primary culture of ovarian surface epithelial cells and ascites-derived ovarian cancer cells from patients. Nat Protoc 1:2643–2649
Frankel A, Rosen K, Filmus J, Kerbel RS (2001) Induction of anoikis and suppression of human ovarian tumor growth in vivo y down-regulation of Bcl-XL1. Cancer Res 61:4837–4841
Sher I, Adham SA, Petrik J, Coomber BL (2009) Autocrine VEGF-A/KDR loop protects epithelial ovarian carcinoma cells from anoikis. Int J Cancer 124:553–561
He X, Ota T, Liu P, Su C, Chien J, Shridhar V (2010) Downregulation of HtrA1 promotes resistance to anoikis and peritoneal dissemination of ovarian cancer cells. Cancer Res 70:3108–3118
Liu J, Yang G, Thompson-Lanza JA, Glassman A, Hayes K, Patterson A, Marquez RT, Auersperg N, Yu Y, Hahn WC, Mills GB, Bast RC Jr (2004) A genetically defined model for human cancer. Cancer Res 64:1655–1663
Burleson KM, Casey RC, Skubitz KM, Pambuccian SE, Oegema TR Jr, Skubitz AP (2004) Ovarian carcinoma spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol Oncol 93:170–181
Burleson KM, Hansen LK, Skubitz AP (2004) Ovarian carcinoma spheroids disaggregate on type I collagen and invade live human mesothelial cell monolayers. Clin Exp Metastasis 21:685–697
Ahmed N, Thompson EW, Quinn MA (2007) Epithelial-mesenchymal inter-conversions in normal ovarian surface epithelium and ovarian carcinomas: an exception to the norm. J Cell Physiol 213:581–588
Sodek KL, Ringuette MJ, Brown TJ (2009) Compact spheroid formation by ovarian cancer cells is associated with contractile behavior and an invasive phenotype. Int J Cancer 124:2060–2070
Gregoire L, Rabah R, Schmelz EM, Munkarah A, Roberts PC, Lancaster WD (2001) Spontaneous malignant transformation of human ovarian surface epithelial cells in vitro. Clin Cancer Res 7:4280–4287
Sasaki R, Narisawa-Saito M, Yugawa T, Fujita M, Tashiro H, Katabuchi H, Kiyono T (2008) Oncogenic transformation of human ovarian surface epithelial cells with defined cellular oncogenes. Carcinogenesis 30:423–431
Roberts PC, Motitillo EP, Baxa AC, Heng HHQ, Doyon-Reale N, Gregoire L, Lancaster WD, Rabah R, Schmelz EM (2005) Sequential molecular and cellular events during neoplastic progression: a mouse syngeneic ovarian cancer model. Neoplasia 7:944–956
Greenaway J, Moorehead R, Shaw P, Petrik J (2008) Epithelial-stromal interaction increases cell proliferation, survival and tumorigenicity in a mouse model of human epithelial ovarian cancer. Gynecol Oncol 108:385–394
Connolly DC, Bao R, Nikitin AY, Stephens KC, Poole TW, Hua X, Harris SS, Vanderhyden BC, Hamilton TC (2003) Female mice chimeric for expression of the simian virus 40 Tag under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Res 63:1389–1397
Hensley H, Quinn BA, Wolf RL, Litwin SL, Mabuchi S, Williams SJ, Williams C, Hamilton TC, Connolly DC (2007) Magnetic resonance imaging for detection and determination of tumor volume in a genetically engineered mouse model of ovarian cancer. Caner Biol Ther 6:1717–1725
Mabuchi S, Altomare DA, Connolly DC, Klein-Szanto A, Litwin S, Hoelzle MK, Hensley HH, Hamilton TC, Testa JR (2007) RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer. Cancer Res 67:2408–2413
Lawrenson K, Benjamin E, Turmaine M, Jacobs I, Gayther S, Dafou D (2009) In vitro three-dimensional modeling of human ovarian surface epithelial cells. Cell Prolif 42:385–393
Jin ZH, Josserand V, Razkin J, Garanger E, Boturyn D, Favrot MC, Dumy P, Coll JL (2006) Noninvasive optical imaging of ovarian metastases using Cy5-labeled RAFT-c(-RGDfk-)4. Mol Imaging 5:188–197
Granot D, Kunz-Schughart LA, Neeman M (2005) Labeling fibroblasts with biotin-BSA-GdDTPA-FAM for tracking of tumor associated stroma by fluorescence and MR imaging. Magn Reson Med 54:789–797
Nunez-Cruz S, Connolly DC, Scholler N (2010) An orthotopic model of serous ovarian cancer in immunocompetent mice for in vivo tumor imaging and monitoring of tumor responses. J Visual Exp 45:1–4
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media, New York
About this protocol
Cite this protocol
Petrik, J.J. (2013). Challenges in Experimental Modeling of Ovarian Cancerogenesis. In: Malek, A., Tchernitsa, O. (eds) Ovarian Cancer. Methods in Molecular Biology, vol 1049. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-547-7_28
Download citation
DOI: https://doi.org/10.1007/978-1-62703-547-7_28
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-546-0
Online ISBN: 978-1-62703-547-7
eBook Packages: Springer Protocols