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

被引：296

作者：

Olivares, Orianne ^{[1
,2
,3
,4
]}

Mayers, Jared R. ^{[5
,6
]}

Gouirand, Victoire ^{[1
,2
,3
]}

Torrence, Margaret E. ^{[5
,6
]}

Gicquel, Tristan ^{[1
,2
,3
]}

Borge, Laurence ^{[1
,2
,3
]}

Lac, Sophie ^{[1
,2
,3
]}

Roques, Julie ^{[1
,2
,3
]}

Lavaut, Marie-Noelle ^{[1
,2
,3
]}

Berthezene, Patrice ^{[1
,2
,3
]}

Rubis, Marion ^{[1
,2
,3
]}

Secq, Veronique ^{[1
,2
,3
]}

Garcia, Stephane ^{[1
,2
,3
]}

Moutardier, Vincent ^{[1
,2
,3
]}

Lombardo, Dominique ^{[7
]}

Iovanna, Juan Lucio ^{[1
,2
,3
]}

Tomasini, Richard ^{[1
,2
,3
]}

Guillaumond, Fabienne ^{[1
,2
,3
]}

Vander Heiden, Matthew G. ^{[5
,6
,8
]}

Vasseur, Sophie ^{[1
,2
,3
]}

机构：

[1] Inst Natl Sante & Rech Med, CRCM, Unite 1068, F-13009 Marseille, France

[2] IPC, F-13009 Marseille, France

[3] CNRS, Unite Mixte Rech UMR 7258, F-13009 Marseille, France

[4] Univ Glasgow, Coll Med Vet & Life Sci, Wolfson Wohl Canc Res Ctr, Inst Canc Sci, Garscube Estate,Switchback Rd, Glasgow G61 1QH, Lanark, Scotland

[5] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[6] MIT, Dept Biol, Cambridge, MA 02139 USA

[7] Aix Marseille Univ, INSERM, CRO2, F-13005 Marseille, France

[8] Dana Farber Canc Inst, Boston, MA 02115 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

INTRAEPITHELIAL NEOPLASIA; RECEPTOR UPARAP/ENDO180; GLUCOSE-METABOLISM; CANCER; TUMORS; HYPOXIA; PATHWAY; KRAS; MICROENVIRONMENT; BIOSYNTHESIS;

D O I：

10.1038/ncomms16031

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14