Epithelial-stromal Interaction Increases Cell Proliferation, Survival and Tumorigenicity in a Mouse Model of Human Epithelial Ovarian Cancer
Abstract
Objective Ovarian cancer is the fourth leading cause of cancer-related deaths among women and is among the least understood of all cancers. The objective of this study was to determine the effect of ovarian epithelial and stromal cell interaction in a mouse model of epithelial ovarian cancer (EOC) that closely resembled the human disease.Methods A mouse model of EOC was generated by orthotopic injection of an ID8 mouse ovarian surface epithelial cell line (MOSEC) under the ovarian bursa of syngeneic mice and tissue was collected to evaluate factors contributing to the formation and development of ovarian tumors.Results By 90 days post-injection, mice were moribund and had developed large primary ovarian tumors, secondary tumors within the peritoneal cavity, and extensive ascites fluid production. Tumors were hypervascularized and were characterized as serous epithelial carcinomatosis, which replicates the most common form of human ovarian cancer. Cells isolated from ascites fluid were more proliferative with increased expression of survival factors compared to original MOSEC cells and cells obtained from the abdomen following intraperitoneal injection. Orthotopic injection of these cells under the ovarian bursa resulted in more aggressive tumorigenesis, with mice becoming moribund at 60 days post-injection compared with 90 days post-injection with the original ID8-MOSEC cell line.Discussion This study describes the generation of an orthotopic, syngeneic model of ovarian cancer, which replicates the phenotype of the human disease. Expression of angiogenic and proliferative factors, and the interaction of epithelial cells with the ovarian stroma are important factors in ovarian tumorigenesis.
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The murine ID8 ovarian cancer cell line has been used for a number of syngeneic mouse models, achieving primary ovarian tumors and ascites within 90 days.
“The murine ID8 ovarian cancer cell line (C57Bl/6 background) (Roby et al., 2000), has been used for a number of syngeneic mouse models, achieving primary ovarian tumors and ascites within 90 days (Greenaway et al., 2008).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Greenaway et al., 2008
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- Authors
- Greenaway, J., Moorehead, R., Shaw, P., & Petrik, J.
- Affiliations
- University of Guelph (CA)
- University Health Network (CA)
- Corresponding author
- Petrik, Jim
- Venue
- Gynecologic Oncology
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 108
- Issue
- 2
- Pages
- 385-394
- ISSN
- 0090-8258 (ISSN-L)
- OpenAlex
- W2086770058
- Cited by
- 100
- References
- 41
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 1 · 2022: 8 · 2021: 2 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 7 · 2013: 6 · 2012: 8
- FWCI
- 6.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gynecologic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ontario Institute for Cancer Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- epithelial ovarian cancer, stromal-epithelial interactions, ovarian stroma, mouse tumor model, carcinogenesis, cell proliferation, cell survival factors, angiogenesis, ascites, peritoneal carcinomatosis, tumor hypervascularization
- MeSH terms
- Animals, Cell Communication, Cell Movement, Disease Models, Animal, Epithelial Cells, Female, Humans, Mice, Inbred C57BL, Ovarian Neoplasms, Biomarkers, Tumor, Stromal Cells, Vascular Endothelial Growth Factor A, Cell Line, Tumor, Cell Growth Processes, Mice
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