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

Olivares, O. et al. (2017) Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nature Communications, 8, 16031. (doi: 10.1038/ncomms16031) (PMID:28685754) (PMCID:PMC5504351)

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 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Olivares, Miss Orianne
• Authors: Olivares, O., Mayers, J. R., Gouirand, V., Torrence, M. E., Gicquel, T., Borge, L., Lac, S., Roques, J., Lavaut, M.-N., Berthezène, P., Rubis, M., Secq, V., Garcia, S., Moutardier, V., Lombardo, D., Iovanna, J. L., Tomasini, R., Guillaumond, F., Vander Heiden, M. G., and Vasseur, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Nature Communications 8:16031
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
65958	1	Identifying Novel Targets for eradication of acute lymphoblastic leukaemia in the central nervous system	Christina Halsey	Office of the Chief Scientist (CSO)	ETM/374	III -IMMUNOLOGY