Abstract B48: Pancreatic cancer cells exhibit heterogeneous glucose and glutamine metabolic dependencies

Abstract

Abstract Pancreatic cancer cells demonstrate altered metabolism that is consistent with amplified aerobic glycolysis, fueled by increased glucose uptake. Concurrently, additional studies have established an enhanced dependence on glutamine to power anabolic processes. Recently, there has been a renewed interest in understanding the altered metabolic requirements of cancer cells with the goal of targeting differential nutrient dependencies for therapeutic gain. We screened a panel of twelve well established and widely studied KRAS mutant pancreatic tumor-derived cell lines, as well as seven low passage KRAS mutant pancreatic patient-derived xenograft (PDX)-established tumor cell lines for the ability to proliferate in growth media deficient in glucose and/or glutamine. While 11 of 12 established cell lines were unable to proliferate in these nutrient-depleted conditions, we identified one (Capan-2) that was capable of proliferation in the complete absence of glucose. By comparison, of the seven PDX-derived cell lines screened, four demonstrated complete glucose or glutamine dependency, whereas one was capable of proliferation in the absence of glutamine and two proliferated in the absence of glucose. Our ongoing studies are focused on elucidating the mechanistic basis for glucose or glutamine independent growth. Defining these mechanisms may identify pharmacologic approaches that target metabolic pathways for the treatment of KRAS mutant pancreatic cancer. Citation Format: Kirsten L. Bryant, Anirban Maitra, Channing J. Der. Pancreatic cancer cells exhibit heterogeneous glucose and glutamine metabolic dependencies. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B48.