Abstract 1537: The extracellular matrix supports pancreatic cancer cell growth under nutrient deprivation

Abstract Pancreatic cancers have a poorly vascularized and nutrient-deficient microenvironment making them more susceptible to nutrient deprivation. Evidence has shown that Pancreatic Ductal Adenocarcinoma (PDAC) cells survive in a nutrient-deprived and hypovascular microenvironment. Here, we investigate the roles of the Extracellular Matrix (ECM) in supporting the growth of PDAC cells in different nutrient-deprivation conditions. Our cell proliferation, microscopy and targeted Mass Spectroscopy metabolomics data showed that Matrigel, but not collagen I, supports the proliferation of PDAC cells in Glucose and Glutamine deprivation conditions, as well as in Tissue Interstitial Fluid Media (TIFM), which has been reported to mimic the physiological nutrient availability in PDAC tumors. In addition, we found that the role of Matrigel in supporting the growth of pancreatic cancer cells is linked to increasing cell proliferation rather than reducing cell death. Importantly, our Targeted Mass spectrometry metabolomics data showed that the Arginine metabolism is upregulated when the cells are grown under starvation on Matrigel compared to plastic. We have identified some genes that are likely to play a role in the upregulation of this metabolic pathway and we are currently using qPCR and Western blotting techniques to identify whether the ECM and/or nutrient availability affect their expression. Finally, we will determine their role in promoting ECM-dependent PDAC cell proliferation under starvation. Overall, our study has established that the ECM can alter the metabolism of PDAC cells to support their cell growth under nutrient-limiting conditions. Citation Format: Ifeoluwa Feyisayo Oyelade, Elena Rainero. The extracellular matrix supports pancreatic cancer cell growth under nutrient deprivation [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 1537.