Epithelial-Stromal Interactions in Induction of Ovarian Cancer in a Mouse Model

摘要

Ovarian cancer can be effectively treated if detected early, but it is generally diagnosed after it has metastasized. This seriously impacts the survival rate of patients, and has also limited our knowledge of the early genetic changes that induce ovarian cancer. Our goal is to develop experimental systems that recapitulate genetic changes that occur during ovarian carcinoma initiation and simulate the complex interactions between ovarian surface epithelial and stromal cells. By introducing various combinations of genetic alterations into the ovarian surface epithelial cells ex vivo and in situ, we demonstrated that certain biochemical pathways can collaborate in ovarian cancer initiation and progression. We also explored the role of stromal cells in ovarian cancer progression and determined that both transformed and untransformed stromal cells are inhibitory to tumor growth. Since ovulation is thought to be directly associated with ovarian tumor initiation, we studied cell proliferation during ovulatory wound repair. We determined that ovulation increases the overall rate of ovarian surface epithelial cell proliferation. However, the ovulatory wound is mostly repaired by cell migration and not by local cell proliferation. Induced ovulation in mice also contributed to the formation of ovarian inclusion cysts, which are thought to be the precursor lesions in ovarian cancer.