Epithelial–stromal interaction increases cell proliferation, survival and tumorigenicity in a mouse model of human epithelial ovarian cancer
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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.
