Abstract 3468: Adrenergic signaling in adipocytes drives ovarian cancer cell invasion

Abstract High grade serous cancer (HGSC) is the most common and lethal ovarian cancer subtype. HGSC can arise from the fallopian tube and habitually metastasizes to the omentum; consequently, we seek to further elucidate the metabolic crosstalk involved in HGSC colonization of omentum. By applying imaging mass spectrometry (IMS) to co-cultures of HGSC cells and omental explants we are able spatially resolve the chemistry produced and identify molecules unique to the HGSC + omentum cultures as compared to non-tumorigenic co-cultures or monocultures. One such molecule is epinephrine which IMS reveals to be produced by the omentum. From this we hypothesize autocrine epinephrine signaling in omental adipocytes liberates fatty acids driving tumor progression. To aid in more mechanistic investigation a human, pre-adipocyte line which forms spheroids and differentiates to mature adipocytes in culture is employed. Analyzed by IMS adipocyte spheroids and co-cultures with HGSC produced epinephrine confirming an omental cell type responsible to be adipocytes. Omental explants and adipocyte spheroids were subjected to treatment with epinephrine (10μM) or propranolol (1μM) and the resulting conditioned media collected. Three HGSC models -MOE PTENshRNA, OVCAR4, and OVCAR8- were treated with conditioned media and their invasive potential measured by Matrigel coated Boyden chamber. Propranolol treated conditioned media from either adipocyte source resulted in significantly decreased invasion compared to control while epinephrine treated omental conditioned media significantly increased MOE PTENshRNA invasion. Untargeted lipidomics performed on treated adipocyte spheroid conditioned media has uncovered lipid species differentially regulated between the epinephrine and propranolol treated conditioned medias including fatty acyls, sterols, and N-acylethanolamides. Current work seeks to explore the impact of epinephrine on sterol biosynthesis, determine if any identified lipid species is sufficient to drive HGSC cell invasion, and identify an upstream HGSC signal inducing epinephrine production in the adipocytes. Overall, we seek to expand our understanding of signaling critical in colonization of the omental metastatic niche and the role of the epinephrine therein. Citation Format: Monica A. Haughan, Carlismari Grundmann, Hannah J. Lusk, Laura M. Sanchez, Joanna E. Burdette. Adrenergic signaling in adipocytes drives ovarian cancer cell invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3468.