Abstract PR-008: Follicular fluid aids in cell adhesion, spreading and shows an age-dependent effect on DNA damage in fallopian tube epithelial cells

Abstract

Abstract Ovarian cancer is the 5th leading cause of cancer related death in women with a low 5-year survival rate. Ovarian cancer is rarely detected early, and likely arises from the fimbriated end of the fallopian tube epithelium (FTE). There is a correlation between ovarian cancer and ovulation whereby ovulation suppression through use of oral contraception or pregnancy reduces the risk of ovarian cancer. Despite the association of ovarian cancer with ovulation, due to the lack of early detection methods, the disease typically presents as late stage, metastatic cancer in post-menopausal women who are no longer ovulating. The goal of this study was to understand how ovulation and the process of aging interact to provide a permissive environment for ovarian cancer initiation and progression in the FTE. The process of ovulation releases follicular fluid and induces the DNA damage response pathway in the FTE, but the role of aging on FTE exposure to follicular fluid has not been tested. De-identified follicular fluid samples were collected from 14 women (7 reproductively young (29-35 years) and 7 reproductively aged (40-44 years)) undergoing ART (Assisted Reproductive Technology) through the Northwestern University Reproductive Tissue Library (NU-RTL). We found that follicular fluid caused DNA damage and lipid oxidation in an age-dependent manner and cell proliferation in a dose-dependent manner in FTE cells. Interestingly, follicular fluid disrupted FTE spheroid formation and instead stimulated attachment and growth on ultra-low attachment plates. Follicular fluid when coated on the surface of the ultra-low plates enhanced FTE cell adhesion, spreading and proliferation. Proteomics analysis of the follicular fluid identified vitronectin, a glycoprotein as the factor responsible for FTE cell attachment and spreading. Overall, this study demonstrated that aging contributed to lipid oxidation and DNA damage of FTE cells and identified vitronectin in the follicular fluid as a protein factor that facilitates FTE cells to detach from 3D spheroids and spread on low attachment surfaces. Citation Format: Amrita Salvi, Wenping Li, Stephanie M. Cologna, Mary Ellen Pavone, Francesca E. Duncan, Joanna E. Burdette. Follicular fluid aids in cell adhesion, spreading and shows an age-dependent effect on DNA damage in fallopian tube epithelial cells [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr PR-008.