Abstract A034: Thermoregulation alters adipose influence of pancreatic cancer growth

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer death in the United States and has an abysmal 5-year overall survival of 12%. A major risk factor for PDAC is obesity- which has increased 12% between 1999-2018 in the United States. This rise correlates with the projection that PDAC is to become the second leading cause of cancer death by 2025. Clinically, reports show obese PDAC patients have a three-month decrease in overall survival when compared to lean PDAC patients. Multiple studies have implicated obese white adipose tissue (WAT) as promoting tumor progression. Yet only one study has investigated the effects of brown adipose tissue (BAT) on PDAC, which exhibited cold-mediated BAT activation steals glucose from the tumor. Aside from potential metabolic regulation, our group discovered that cold-mediated activated BAT elicited the release of anti-tumorigenic factors. We discovered this by exposing diet-induced obese mice to a subthermal environment via a thermogenic shift (TS) from thermoneutral (TN) housing. The TS BAT-conditioned media (CM) inhibited PDAC cell proliferation (EdU) and increased apoptosis (via cleaved caspase-3). Using a cytokine array, we identified endostatin as the most upregulated molecule in TS BAT-CM compared to TN BAT-CM. Incubation of PDAC cell lines with recombinant endostatin showed increased cleaved caspase-3. A shotgun-based proteomics screen uncovered novel endostatin binding partners and signaling mediators. In conclusion, we have identified a novel anti-tumorigenic role for activated BAT that further suggests its importance in relation to PDAC progression. Citation Format: Austin Eades, Bailey Bye, R. McKinnon Walsh, Michael VanSaun. Thermoregulation alters adipose influence of pancreatic cancer growth [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A034.