Histologic evaluation of the decellularized ovary as a model for the study of ovarian cancer cell adhesion and expansion

This study will determine the effects of decellularization on the ECM structure and composition of the mouse ovary, which is critical for future experiments utilizing the decellularized mouse ovary as a model. Moreover, this work will characterize decellularized ovaries across an age-range, setting the stage for future aging studies. Here, I will probe the mechanism by which the aging ovarian microenvironment contributes to ovarian cancer pathogenesis. Should age-dependent alterations to the ovarian ECM influence cancer cell adhesion and expansion, future studies will test strategies that curtail fibrotic remodeling as therapies for ovarian cancer. As most current research of ovarian cancer metastasis focuses on secondary metastasis to peritoneal organs, this work will play an important role in advancing knowledge of critical steps involved in the initial HGSOC colonization of the ovary. Significance of ovarian cancer: Ovarian cancer is the fifth leading cause of cancer deaths in women in the U.S., with more than 20,000 new cases and approximately 14,000 deaths every year. High-grade serous ovarian carcinoma (HGSOC) is the most common and lethal form of ovarian cancer, accounting for 70% of cases and 90% of deaths. HGSOC is most often diagnosed as late-stage, metastatic cancer in post-menopausal women. Despite the prevalence and high mortality associated with ovarian cancer, precise mechanisms of how the disease is initiated and why it expands in the ovary remain unclear. Significance of the aging ovary: HGSOC is not often diagnosed until after menopause, suggesting that the aging ovary may provide a unique anatomical niche for tumor expansion. The ovarian extracellular matrix (ECM) undergoes significant remodeling with age. Work from our lab has shown that the ovarian ECM becomes fibrotic with advanced reproductive age, specifically accumulating increased levels of collagen I and III. This accumulation of collagen also changes the mechanical properties of th