Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions

• DOI: 10.1038/ncomms16031
• Publication Date: 2017-07-07T09:10:10Z
• Authors: Orianne Olivares; Jared R. Mayers; Victoire Gouirand; Margaret E. Torrence; Tristan Gicquel; Laurence Borge; Sophie Lac; Julie Roques; Marie-Noëlle Lavaut; Patrice Berthezène; Marion Rubis; Veronique Secq; Stéphane Garcia; Vincent Moutardier; Dominique Lombardo; Juan Lucio Iovanna; Richard Tomasini; Fabienne Guillaumond; Matthew G. Vander...; Sophie Vasseur
• Keywords: Male; 0301 basic medicine; Proline; Cell Survival; [SDV]Life Sciences [q-bio]; Science; Procollagen-Proline Dioxygenase; [SDV.CAN]Life Sciences [q-bio]/Cancer; Mice, Transgenic; Article; Mice; 03 medical and health sciences; [SDV.CAN] Life Sciences [q-bio]/Cancer; Cell Line, Tumor; Matrix Metalloproteinase 13; Proline Oxidase; Animals; Humans; Cell Proliferation; Q; Biological Transport; Extracellular Matrix; [SDV] Life Sciences [q-bio]; Gene Expression Regulation, Neoplastic; Pancreatic Neoplasms; Matrix Metalloproteinase 9; Collagen; Neoplasm Transplantation; Carcinoma, Pancreatic Ductal

Abstract Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism is needed for tumour survive this environment, but the metabolic modifications that allow endure these conditions incompletely understood. Here we demonstrate collagen serves as proline reservoir use nutrient source when other fuels limited. We show able take up fragments, which can promote cell survival under limited conditions, collagen-derived metabolism. Finally, oxidase (PRODH1) required proliferation vitro vivo . Collectively, our results indicate extracellular matrix represents highlighting flexibility of cancer.