Journal Article

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

Vasseur, Sophie, Berthezène, Patrice, Guillaumond, Fabienne, Tomasini, Richard, Gouirand, Victoire, Lombardo, Dominique, Moutardier, Vincent, Garcia, Stéphane, Lac, Sophie, Mayers, Jared R., Torrence, Margaret E., Gicquel, Tristan, Olivares, Orianne, Rubis, Marion, Roques, Julie, Lavaut, Marie-Noëlle, Borge, Laurence, Secq, Veronique, Vander Heiden, Matthew G., Iovanna, Juan Lucio

2017

Overview

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 cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited. We show PDAC cells are able to take up collagen fragments, which can promote PDAC cell survival under nutrient limited conditions, and that collagen-derived proline contributes to PDAC cell metabolism. Finally, we show that proline oxidase (PRODH1) is required for PDAC cell proliferation in vitro and in vivo . Collectively, our results indicate that PDAC extracellular matrix represents a nutrient reservoir for tumour cells highlighting the metabolic flexibility of this cancer. Cancer cells adapt their metabolism to survive limited nutrient availability. Here, the authors show that in conditions of limited glucose or glutamine availability, pancreatic ductal adenocarcinoma cells can use collagen-derived proline to foster the TCA cycle and allow cell survival both in vitro and in vivo .

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/105 / 13/106 / 13/31 / 13/51 / 13/95 / 631/67/1504/1713 / 631/67/2327 / Adenocarcinoma / Animals / Biological Transport / Cancer / Carcinoma, Pancreatic Ductal - genetics / Carcinoma, Pancreatic Ductal - metabolism / Carcinoma, Pancreatic Ductal - pathology / Cell Line, Tumor / Cell Proliferation / Cell Survival / Collagen / Collagen - chemistry / Collagen - metabolism / Extracellular matrix / Extracellular Matrix - chemistry / Extracellular Matrix - metabolism / Fragments / Gene Expression Regulation, Neoplastic / Humanities and Social Sciences / Humans / In vitro methods and tests / Life Sciences / Male / Matrix Metalloproteinase 13 - genetics / Matrix Metalloproteinase 13 - metabolism / Matrix Metalloproteinase 9 - genetics / Matrix Metalloproteinase 9 - metabolism / Metabolism / Mice / Mice, Transgenic / multidisciplinary / Neoplasm Transplantation / Nutrients / Oxidase / Pancreas / Pancreatic cancer / Pancreatic Neoplasms - genetics / Pancreatic Neoplasms - metabolism / Pancreatic Neoplasms - pathology / Procollagen-Proline Dioxygenase - genetics / Procollagen-Proline Dioxygenase - metabolism / Proline / Proline - metabolism / Proline oxidase / Proline Oxidase - genetics / Proline Oxidase - metabolism / Reservoirs / Science / Science (multidisciplinary) / Signal Transduction / Survival / Tumors