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Epithelial ovarian cancer experimental models

Abstract

Epithelial ovarian cancer (OvCa) is associated with high mortality and, as the majority (>75%) of women with OvCa have metastatic disease at the time of diagnosis, rates of survival have not changed appreciably over 30 years. A mechanistic understanding of OvCa initiation and progression is hindered by the complexity of genetic and/or environmental initiating events and lack of clarity regarding the cell(s) or tissue(s) of origin. Metastasis of OvCa involves direct extension or exfoliation of cells and cellular aggregates into the peritoneal cavity, survival of matrix-detached cells in a complex ascites fluid phase and subsequent adhesion to the mesothelium lining covering abdominal organs to establish secondary lesions containing host stromal and inflammatory components. Development of experimental models to recapitulate this unique mechanism of metastasis presents a remarkable scientific challenge, and many approaches used to study other solid tumors (for example, lung, colon and breast) are not transferable to OvCa research given the distinct metastasis pattern and unique tumor microenvironment (TME). This review will discuss recent progress in the development and refinement of experimental models to study OvCa. Novel cellular, three-dimensional organotypic, and ex vivo models are considered and the current in vivo models summarized. The review critically evaluates currently available genetic mouse models of OvCa, the emergence of xenopatients and the utility of the hen model to study OvCa prevention, tumorigenesis, metastasis and chemoresistance. As these new approaches more accurately recapitulate the complex TME, it is predicted that new opportunities for enhanced understanding of disease progression, metastasis and therapeutic response will emerge.

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Abbreviations

ECM:

extracellular matrix

GEMM:

genetically engineered mouse model

IOSE:

immortalized ovarian surface epithelium

i.p.:

intraperitoneal

LSL:

Lox-STOP-Lox

MISRII:

Müllerian inhibiting substance II receptor

MOSE:

mouse ovarian surface epithelium

OvCa:

ovarian cancer

RB:

retinoblastoma

s.c.:

subcutaneous

TME:

tumor microenvironment

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Acknowledgements

The impetus for this collaborative compendium arose from the inaugural workshop of the Indiana-Illinois End Epithelial Ovarian Cancer Coalition (IIEEOC) held at the University of Notre Dame in 2012. The IIEEOCC Workshop was supported by the Harper Cancer Research Institute, the University of Notre Dame, the Indiana University Simon Cancer Center and the Indiana Clinical and Translational Sciences Institute. We gratefully acknowledge the lively and informative discussion contributed by all workshop participants. Funding for our work was provided by National Institutes of Health/National Cancer Institute Research Grants, CA086984 (MSS), CA109545 (MSS); CA085289 (KN), CA085289 (KN), the Integrative Cancer Biology Program CA1113001 (KN) and an Ovarian Cancer Research Fund (PPD/IU) to KN and DM; NIH/National Center for Complementary and Alternative Medicine grants AT00408 and AT005295 (BH); National Cancer Institute Award CA133915 (BH); American Institute for Cancer Research 06-A043 (BH); NIH/NCI CA111882 (EL) and an Ovarian Cancer Research Fund (PPD/UofC) to EL. JB was supported by the Ovarian Cancer Research Fund Liz Tilberis Ovarian Cancer Scholar Award (L/T UIC), the American Cancer Society Illinois Division Research Grant RSG-12-230-01-TBG and the Department of Defense OC110133. PH was supported by the Mayo Clinic SPORE in Ovarian Cancer-CA136393.

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Correspondence to E Lengyel or M S Stack.

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Lengyel, E., Burdette, J., Kenny, H. et al. Epithelial ovarian cancer experimental models. Oncogene 33, 3619–3633 (2014). https://doi.org/10.1038/onc.2013.321

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Keywords

  • ovarian cancer
  • mouse model
  • cell lines
  • hen
  • organotypic models
  • metastasis

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