Pancreatic Tumor Microenvironment Maintains Tumor Growth through Nucleosides Secretion

Cancer-associated fibroblasts (CAFs) are one of the most prominent and active components in the pancreatic tumor microenvironment. Our data show that CAFs are critical for PDAC survival upon glutamine deprivation. Specifically, we uncovered a role for nucleosides, which are secreted by CAFs through autophagy in an NUFIP1-depenent manner, increased glucose utilization and promoted growth of PDAC. Moreover, we demonstrate that CAF-derived nucleosides induced glucose consumption under glutamine-deprived conditions and displayed a dependence on MYC. Using an orthotopic mouse model of PDAC, we found that inhibiting nucleoside secretion by targeting NUFIP1 in the stroma reduced tumor weight. This finding highlights a previously unappreciated metabolic network within pancreatic tumors in which diverse nutrients are used to promote growth in an austere tumor microenvironment. 2 samples.14837 PDAC cells were treated with CAF conditional medium or 14837 conditional medium. Cells' RNA was harvested using Trizol reagent. 2 ug of total RNA is used for the construction of sequencing libraries by Novaseq 6000.