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

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

Nature communications (2017-07-08)
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 Heiden, Sophie Vasseur
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-PRODH antibody produced in goat, affinity isolated antibody, buffered aqueous solution
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Anti-MAP Kinase (ERK-1, ERK-2) antibody produced in rabbit, whole antiserum
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Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, ascites fluid
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Collagen from Engelbreth-Holm-Swarm murine sarcoma basement membrane, Type IV (Miller), lyophilized powder, BioReagent, suitable for cell culture
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Monoclonal Anti-MAP Kinase, Activated (Diphosphorylated ERK-1&2) antibody produced in mouse, clone MAPK-YT, ascites fluid
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Anti-Mouse Collagen Type I Antibody, Chemicon®, from rabbit
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Triton X-100, laboratory grade
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Collagen from calf skin, Bornstein and Traub Type I, (0.1% solution in 0.1 M acetic acid), aseptically processed, BioReagent, suitable for cell culture