Abstract B032: Probing the molecular crosstalk between ovarian cancer and omentum

Abstract Ovarian cancer (OC) is the 5th leading cause of cancer death in women despite being considered rare, highlighting the critical need to better understand the mechanisms of pathogenesis and progression. High grade serous OC, the most prevalent OC subtype, frequently metastasizes to the omentum. Building off previous work using an imaging mass spectrometry (IMS) co-culture system to uncover metabolomic changes in primary metastasis, we are now probing the molecular crosstalk between the omentum and OC cells. Our IMS co-culture system identifies molecules produced in co-culture of tumorigenic MOE PTENshRNA or vector control MOE PTENSCR cells and explants. IMS revealed multiple signals, including epinephrine (EPI), unique to the MOE PTENshRNA + omentum condition. Clinical data shows stress and increased expression of ADRβ2, an EPI receptor, are correlated with poorer survival. However, no significant changes were observed in EPI (10mM) treated MOE PTENshRNA invasiveness investigated via Boyden chamber assay. EPI signaling through ADRβ2 can induce lipolysis and propranolol treatment, antagonizing ADRβ2, has shown partial deactivation of OC stimulated lipolysis. We hypothesize EPI may be an autocrine signal produced by the omentum liberating fatty acids and driving tumor progression. To test this, we began examining an immortalized, human pre-adipocyte line (VNPAD 30315) for mechanistic studies. VNPAD 30315 can be differentiated into adipocytes and forms spheroids more accurately simulating in vivo fatty tissues compared to 2D culture. Successfully differentiated spheroids have been generated and spheroid conditioned media (CM) increases invasion like omentum CM. Preliminary results suggest spheroids produce results similar to murine and human omentum explants in IMS co-culture. Currently we are exploring the effects of EPI on the spheroids and adipocyte CM on tumorigenic models. Overall, we are working to identify signals in omental metastasis with our IMS co-culture system and to determine their mechanisms in vitro with a 3D adipocyte model. Citation Format: Monica A. Haughan, Hannah Lusk, Tova M. Bergsten, Sarah E. Levy, Aloysius J. Klingelhutz, Laura M. Sanchez, Joanna E. Burdette. Probing the molecular crosstalk between ovarian cancer and omentum 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 Suppl₂): Abstract nr B032.