Abstract 80: Integrin driven adhesion in ovarian cancer

Abstract Ovarian cancer is the fifth leading cause of cancer-related deaths in women due to late-stage diagnosis, reducing the survival rate to 30%. During dissemination, ovarian cancer cellsexfoliate from the primary tumor and aggregate to form spheroids in the peritoneal cavity. Peritonealaggregation enhances the survival of cancer cells by mitophagy, reduced metabolism, andproliferation. However, as spheroids adhere to secondary sites, mitochondrial function is restoredby mitobiogenesis, with increased metabolism and proliferation. These findings strongly suggest aswitch from mitophagy in spheroids to mitobiogenesis upon adhesion. However, the mechanism bywhich adhesion induces mitobiogenesis remains unknown. Therefore, our objective is to identifykey adhesion receptors, with a focus on integrins that activate adhesion and downstream signalingcascades. To investigate changes in integrin expression, we mimicked three major stages ofovarian cancer progression by developing adherent, spheroid, and adherent spheroid stages usingmouse ovarian surface epithelial (MOSE) cell lines. These represented the benign (MOSE-E) stage, as well as slow-developing (MOSE-L) and fast-developing (MOSE-LTICv) disease in biologicallyrelevant conditions. We identified integrin and adhesion-related gene expression levels via RT-qPCR. Western blotting and confocal microscopy were used to observe protein expression andlocalization throughout ovarian cancer progression. Drug treatment was done to observe the effectof integrin inhibition on spheroid aggregation and adhesion to secondary sites. Our finding revealeddistinct expression changes of different integrins during aggregation and adhesion, as well asspecific changes of other adhesion molecules, ECM, and their regulators indicating specific rolesin metastatic dissemination and implantation. This was further confirmed with specific integrininhibitors that were effective in preventing aggregation and spheroid adhesion to secondary sitesindicating distinct roles of integrins during the metastatic stages. Overall, this project will aid inidentifying integrin and integrin drug targets to develop new metastatic treatments, ultimately aimingto reduce mortality in women with ovarian cancer. Citation Format: Nazia Bano, Isabelle Lewis, Malaika Amin, Eva M. Schmelz. Integrin driven adhesion in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 80.