Volume 42 Issue 2
Mar.  2021
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Sergey Karakashev, Ru-Gang Zhang. Mouse models of epithelial ovarian cancer for preclinical studies. Zoological Research, 2021, 42(2): 153-160. doi: 10.24272/j.issn.2095-8137.2020.382
Citation: Sergey Karakashev, Ru-Gang Zhang. Mouse models of epithelial ovarian cancer for preclinical studies. Zoological Research, 2021, 42(2): 153-160. doi: 10.24272/j.issn.2095-8137.2020.382

Mouse models of epithelial ovarian cancer for preclinical studies

doi: 10.24272/j.issn.2095-8137.2020.382
Funds:  This work was supported by the US National Institutes of Health (R01CA160331, R01CA163377, R01CA202919, R01CA239128, P01AG031862, P50CA228991 to R.G.Z. and K99CA241395 to S.K.), US Department of Defense (OC180109 and OC190181 to R.G.Z.). The Honorable Tina Brozman Foundation for Ovarian Cancer Research (to R.G.Z.), and Ovarian Cancer Research Alliance Collaborative Research Development Grant (to R.G.Z.). Core facilities support was provided by a Cancer Centre Support Grant (CA010815) to the Wistar Institute
More Information
  • Corresponding author: E-mail: rzhang@wistar.org
  • Received Date: 2020-12-28
  • Accepted Date: 2021-01-26
  • Published Online: 2021-01-28
  • Publish Date: 2021-03-18
  • Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer-related mortality in the developed world. EOC is a heterogeneous disease represented by several histological and molecular subtypes. Therefore, exploration of relevant preclinical animal models that consider the heterogenic nature of EOC is of great importance for the development of novel therapeutic strategies that can be translated clinically to combat this devastating disease. In this review, we discuss recent progress in the development of preclinical mouse models for EOC study as well as their advantages and limitations.
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  • [1]
    Ahmed N, Stenvers KL. 2013. Getting to know ovarian cancer ascites: opportunities for targeted therapy-based translational research. Frontiers in Oncology, 3: 256.
    Alhilli MM, Becker MA, Weroha SJ, Flatten KS, Hurley RM, Harrell MI, et al. 2016. In vivo anti-tumor activity of the PARP inhibitor niraparib in homologous recombination deficient and proficient ovarian carcinoma. Gynecologic Oncology, 143(2): 379−388. doi: 10.1016/j.ygyno.2016.08.328
    Bajrami I, Frankum JR, Konde A, Miller RE, Rehman FL, Brough R, et al. 2014. Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity. Cancer Research, 74(1): 287−297. doi: 10.1158/0008-5472.CAN-13-2541
    Beaufort CM, Helmijr JCA, Piskorz AM, Hoogstraat M, Ruigrok-Ritstier K, Besselink N, et al. 2014. Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes. PLoS One, 9(9): e103988. doi: 10.1371/journal.pone.0103988
    Byrne AT, Ross L, Holash J, Nakanishi M, Hu LM, Hofmann JI, et al. 2003. Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clinical Cancer Research, 9(15): 5721−5728.
    Chandler RL, Damrauer JS, Raab JR, Schisler JC, Wilkerson MD, Didion JP, et al. 2015. Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling. Nature Communications, 6(1): 6118. doi: 10.1038/ncomms7118
    Choi Y, Lee S, Kim K, Kim SH, Chung YJ, Lee C. 2018. Studying cancer immunotherapy using patient-derived xenografts (PDXs) in humanized mice. Experimental & Molecular Medicine, 50(8): 99.
    Connolly DC, Bao RD, Nikitin AY, Stephens KC, Poole TW, Hua X, et al. 2003. Female mice chimeric for expression of the simian virus 40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Research, 63(6): 1389−1397.
    Cordero AB, Kwon Y, Hua X, Godwin AK. 2010. In vivo imaging and therapeutic treatments in an orthotopic mouse model of ovarian cancer. Journal of Visualized Experiments, (42): 2125.
    Cordier AC, Haumont SM. 1980. Development of thymus, parathyroids, and ultimo-branchial bodies in NMRI and nude mice. American Journal of Anatomy, 157(3): 227−263. doi: 10.1002/aja.1001570303
    Domcke S, Sinha R, Levine DA, Sander C, Schultz N. 2013. Evaluating cell lines as tumour models by comparison of genomic profiles. Nature Communications, 4(1): 2126. doi: 10.1038/ncomms3126
    Flesken-Nikitin A, Choi KC, Eng JP, Shmidt EN, Nikitin AY. 2003. Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium. Cancer Research, 63(13): 3459−3463.
    Fu X, Hoffman RM. 1993. Human ovarian carcinoma metastatic models constructed in nude mice by orthotopic transplantation of histologically-intact patient specimens. Anticancer Research, 13(2): 283−286.
    Gitto SB, Kim H, Rafail S, Omran DK, Medvedev S, Kinose Y, et al. 2020. An autologous humanized patient-derived-xenograft platform to evaluate immunotherapy in ovarian cancer. Gynecologic Oncology, 156(1): 222−232. doi: 10.1016/j.ygyno.2019.10.011
    Guan B, Rahmanto YS, Wu RC, Wang YH, Wang Z, Wang TL, et al. 2014. Roles of deletion of Arid1a, a tumor suppressor, in mouse ovarian tumorigenesis. Journal of the National Cancer Institute, 106(7): dju146.
    Hansen JM, Coleman RL, Sood AK. 2016. Targeting the tumour microenvironment in ovarian cancer. European Journal of Cancer, 56: 131−143. doi: 10.1016/j.ejca.2015.12.016
    Hardy S, Kitamura M, Harris-Stansil T, Dai Y, Phipps ML. 1997. Construction of adenovirus vectors through Cre-lox recombination. Journal of Virology, 71(3): 1842−1849. doi: 10.1128/JVI.71.3.1842-1849.1997
    Heo EJ, Cho YJ, Cho WC, Hong JE, Jeon HK, Oh DY, et al. 2017. Patient-derived xenograft models of epithelial ovarian cancer for preclinical studies. Cancer Research and Treatment, 49(4): 915−926. doi: 10.4143/crt.2016.322
    Hernandez L, Kim MK, Lyle LT, Bunch KP, House CD, Ning F, et al. 2016. Characterization of ovarian cancer cell lines as in vivo models for preclinical studies. Gynecologic Oncology, 142(2): 332−340. doi: 10.1016/j.ygyno.2016.05.028
    Hoess RH, Abremski K. 1985. Mechanism of strand cleavage and exchange in the Cre-lox site-specific recombination system. Journal of Molecular Biology, 181(3): 351−362. doi: 10.1016/0022-2836(85)90224-4
    House CD, Hernandez L, Annunziata CM. 2014. Recent technological advances in using mouse models to study ovarian cancer. Frontiers in Oncology, 4: 26.
    Hu LM, Hofmann J, Holash J, Yancopoulos GD, Sood AK, Jaffe RB. 2005. Vascular endothelial growth factor trap combined with paclitaxel strikingly inhibits tumor and ascites, prolonging survival in a human ovarian cancer model. Clinical Cancer Research, 11(19 Pt 1): 6966−6971.
    Ince TA, Sousa AD, Jones MA, Harrell JC, Agoston ES, Krohn M, et al. 2015. Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours. Nature Communications, 6(1): 7419. doi: 10.1038/ncomms8419
    Iyer S, Zhang S, Yucel S, Horn H, Smith SG, Reinhardt F, et al. 2020. Genetically defined syngeneic mouse models of ovarian cancer as tools for the discovery of combination immunotherapy. Cancer Discovery, doi: 10.1158/2159-8290.CD-20-0818.
    Izumchenko E, Paz K, Ciznadija D, Sloma I, Katz A, Vasquez-Dunddel D, et al. 2017. Patient-derived xenografts effectively capture responses to oncology therapy in a heterogeneous cohort of patients with solid tumors. Annual Oncology, 28(10): 2595−2605. doi: 10.1093/annonc/mdx416
    Karnezis AN, Cho KR. 2017. Preclinical models of ovarian cancer: pathogenesis, problems, and implications for prevention. Clinical Obstetrics and Gynecology, 60(4): 789−800. doi: 10.1097/GRF.0000000000000312
    Kiguchi K, Kubota T, Aoki D, Udagawa Y, Yamanouchi S, Saga M, et al. 1998. A patient-like orthotopic implantation nude mouse model of highly metastatic human ovarian cancer. Clinical & Experimental Metastasis, 16(8): 751−756.
    Kim J, Coffey DM, Creighton CJ, Yu ZF, Hawkins SM, Matzuk MM. 2012. High-grade serous ovarian cancer arises from fallopian tube in a mouse model. Proceedings of the National Academy of Sciences of the United States of America, 109(10): 3921−3926. doi: 10.1073/pnas.1117135109
    Kinross KM, Montgomery KG, Kleinschmidt M, Waring P, Ivetac I, Tikoo A, et al. 2012. An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice. The Journal of Clinical Investigation, 122(2): 553−557. doi: 10.1172/JCI59309
    Kortmann U, Mcalpine JN, Xue H, Guan J, Ha G, Tully S, et al. 2011. Tumor growth inhibition by olaparib in BRCA2 germline-mutated patient-derived ovarian cancer tissue xenografts. Clinical Cancer Research, 17(4): 783−791. doi: 10.1158/1078-0432.CCR-10-1382
    Kurman RJ, Shih I M. 2010. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. The American Journal of Surgical Pathology, 34(3): 433−443. doi: 10.1097/PAS.0b013e3181cf3d79
    Kurman RJ, Shih I M. 2011. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer-shifting the paradigm. Human Pathology, 42(7): 918−931. doi: 10.1016/j.humpath.2011.03.003
    Lengyel E, Burdette JE, Kenny HA, Matei D, Pilrose J, Haluska P, et al. 2014. Epithelial ovarian cancer experimental models. Oncogene, 33(28): 3619−3633. doi: 10.1038/onc.2013.321
    Marcotte R, Brown KR, Suarez F, Sayad A, Karamboulas K, Krzyzanowski PM, et al. 2012. Essential gene profiles in breast, pancreatic, and ovarian cancer cells. Cancer Discovery, 2(2): 172−189. doi: 10.1158/2159-8290.CD-11-0224
    Metzger D, Chambon P. 2001. Site- and time-specific gene targeting in the mouse. Methods, 24(1): 71−80. doi: 10.1006/meth.2001.1159
    Mou HW, Kennedy Z, Anderson DG, Yin H, Xue W. 2015. Precision cancer mouse models through genome editing with CRISPR-Cas9. Genome Medicine, 7(1): 53. doi: 10.1186/s13073-015-0178-7
    Perets R, Wyant GA, Muto KW, Bijron JG, Poole BB, Chin KT, et al. 2013. Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models. Cancer Cell, 24(6): 751−765. doi: 10.1016/j.ccr.2013.10.013
    Pla M, Mahouy G. 1991. The SCID mouse. Nouvelle Revue Francaise D'hematologie, 33(6): 489−491.
    Ricci F, Bizzaro F, Cesca M, Guffanti F, Ganzinelli M, Decio A, et al. 2014. Patient-derived ovarian tumor xenografts recapitulate human clinicopathology and genetic alterations. Cancer Research, 74(23): 6980−6990. doi: 10.1158/0008-5472.CAN-14-0274
    Roby KF, Taylor CC, Sweetwood JP, Cheng Y, Pace JL, Tawfik O, et al. 2000. Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogenesis, 21(4): 585−591. doi: 10.1093/carcin/21.4.585
    Said N, Socha MJ, Olearczyk JJ, Elmarakby AA, Imig JD, Motamed K. 2007. Normalization of the ovarian cancer microenvironment by SPARC. Molecular Cancer Research, 5(10): 1015−1030. doi: 10.1158/1541-7786.MCR-07-0001
    Shaw TJ, Senterman MK, Dawson K, Crane CA, Vanderhyden BC. 2004. Characterization of intraperitoneal, orthotopic, and metastatic xenograft models of human ovarian cancer. Molecular Therapy, 10(6): 1032−1042. doi: 10.1016/j.ymthe.2004.08.013
    Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen XH, Chaleff S, et al. 2005. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2Rγnull mice engrafted with mobilized human hemopoietic stem cells. The Journal of Immunology, 174(10): 6477−6489. doi: 10.4049/jimmunol.174.10.6477
    Siegel RL, Miller KD, Jemal A. 2020. Cancer statistics, 2020. CA: A Cancer Journal for Clinicians, 70(1): 7−30. doi: 10.3322/caac.21590
    The Cancer Genome Atlas Research Network. 2011. Integrated genomic analyses of ovarian carcinoma. Nature, 474(7353): 609−615. doi: 10.1038/nature10166
    Topp MD, Hartley L, Cook M, Heong V, Boehm E, McShane L, et al. 2014. Molecular correlates of platinum response in human high-grade serous ovarian cancer patient-derived xenografts. Molecular Oncology, 8(3): 656−668. doi: 10.1016/j.molonc.2014.01.008
    Torre LA, Trabert B, Desantis CE, Miller KD, Samimi G, Runowicz CD, et al. 2018. Ovarian cancer statistics, 2018. CA: A Cancer Journal for Clinicians, 68(4): 284−296. doi: 10.3322/caac.21456
    Walton J, Blagih J, Ennis D, Leung E, Dowson S, Farquharson M, et al. 2016. CRISPR/Cas9-mediated Trp53 and Brca2 knockout to generate improved murine models of ovarian high-grade serous carcinoma. Cancer Research, 76(20): 6118−6129. doi: 10.1158/0008-5472.CAN-16-1272
    Ward BG, Wallace K, Shepherd JH, Balkwill FR. 1987. Intraperitoneal xenografts of human epithelial ovarian cancer in nude mice. Cancer Research, 47(10): 2662−2667.
    Wiegand KC, Hennessy BT, Leung S, Wang YM, Ju ZL, McGahren M, et al. 2014. A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation. BMC Cancer, 14(1): 120. doi: 10.1186/1471-2407-14-120
    Wiegand KC, Shah SP, Al-Agha OM, Zhao YJ, Tse K, Zeng T, et al. 2010. ARID1A mutations in endometriosis-associated ovarian carcinomas. New England Journal of Medicine, 363(16): 1532−1543. doi: 10.1056/NEJMoa1008433
    Wu R, Hendrix-Lucas N, Kuick R, Zhai YL, Schwartz DR, Akyol A, et al. 2007. Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/β-catenin and PI3K/Pten signaling pathways. Cancer Cell, 11(4): 321−333. doi: 10.1016/j.ccr.2007.02.016
    Wu R, Zhai YL, Kuick R, Karnezis AN, Garcia P, Naseem A, et al. 2016. Impact of oviductal versus ovarian epithelial cell of origin on ovarian endometrioid carcinoma phenotype in the mouse. The Journal of Pathology, 240(3): 341−351. doi: 10.1002/path.4783
    Xing DY, Orsulic S. 2006. A mouse model for the molecular characterization of brca1-associated ovarian carcinoma. Cancer Research, 66(18): 8949−8953. doi: 10.1158/0008-5472.CAN-06-1495
    Zhai YL, Kuick R, Tipton C, Wu R, Sessine M, Wang Z, et al. 2016. Arid1a inactivation in an Apc- and Pten-defective mouse ovarian cancer model enhances epithelial differentiation and prolongs survival. The Journal of Pathology, 238(1): 21−30. doi: 10.1002/path.4599
    Zhai YL, Wu R, Kuick R, Sessine MS, Schulman S, Green M, et al. 2017. High-grade serous carcinomas arise in the mouse oviduct via defects linked to the human disease. The Journal of Pathology, 243(1): 16−25. doi: 10.1002/path.4927
    Zhang S, Iyer S, Ran H, Dolgalev I, Gu SQ, Wei W, et al. 2021. Genetically defined, syngeneic organoid platform for developing combination therapies for ovarian cancer. Cancer Discovery, doi: 10.1158/2159-8290.CD-20-0455.
    Zhu HR, Bengsch F, Svoronos N, Rutkowski MR, Bitler BG, Allegrezza MJ, et al. 2016. BET bromodomain inhibition promotes anti-tumor immunity by suppressing PD-L1 expression. Cell Reports, 16(11): 2829−2837. doi: 10.1016/j.celrep.2016.08.032
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