Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions
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...
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/113569 https://orcid.org/0000-0002-8607-1787 https://orcid.org/0000-0002-6702-4192 |
| _version_ | 1826199201090895872 |
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| author | Olivares, Orianne Mayers, Jared R. Gouirand, Victoire Torrence, Margaret E. Gicquel, Tristan Borge, Laurence Lac, Sophie Roques, Julie Lavaut, Marie-Noëlle Berthezène, Patrice Rubis, Marion Secq, Veronique Garcia, Stéphane Moutardier, Vincent Lombardo, Dominique Iovanna, Juan Lucio Tomasini, Richard Guillaumond, Fabienne Vander Heiden, Matthew G. Vasseur, Sophie |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Olivares, Orianne Mayers, Jared R. Gouirand, Victoire Torrence, Margaret E. Gicquel, Tristan Borge, Laurence Lac, Sophie Roques, Julie Lavaut, Marie-Noëlle Berthezène, Patrice Rubis, Marion Secq, Veronique Garcia, Stéphane Moutardier, Vincent Lombardo, Dominique Iovanna, Juan Lucio Tomasini, Richard Guillaumond, Fabienne Vander Heiden, Matthew G. Vasseur, Sophie |
| author_sort | Olivares, Orianne |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:16:02Z |
| format | Article |
| id | mit-1721.1/113569 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:16:02Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1135692022-10-01T02:29:06Z Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions Olivares, Orianne Mayers, Jared R. Gouirand, Victoire Torrence, Margaret E. Gicquel, Tristan Borge, Laurence Lac, Sophie Roques, Julie Lavaut, Marie-Noëlle Berthezène, Patrice Rubis, Marion Secq, Veronique Garcia, Stéphane Moutardier, Vincent Lombardo, Dominique Iovanna, Juan Lucio Tomasini, Richard Guillaumond, Fabienne Vander Heiden, Matthew G. Vasseur, Sophie Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Mayers, Jared R. Torrence, Margaret E. Vander Heiden, Matthew G. 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. 2018-02-12T15:46:57Z 2018-02-12T15:46:57Z 2017-07 2016-01 2018-02-02T19:30:55Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/113569 Olivares, Orianne et al. “Collagen-Derived Proline Promotes Pancreatic Ductal Adenocarcinoma Cell Survival Under Nutrient Limited Conditions.” Nature Communications 8 (July 2017): 16031 © 2017 Author(s) https://orcid.org/0000-0002-8607-1787 https://orcid.org/0000-0002-6702-4192 http://dx.doi.org/10.1038/NCOMMS16031 Nature Communications Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature Communications |
| spellingShingle | Olivares, Orianne Mayers, Jared R. Gouirand, Victoire Torrence, Margaret E. Gicquel, Tristan Borge, Laurence Lac, Sophie Roques, Julie Lavaut, Marie-Noëlle Berthezène, Patrice Rubis, Marion Secq, Veronique Garcia, Stéphane Moutardier, Vincent Lombardo, Dominique Iovanna, Juan Lucio Tomasini, Richard Guillaumond, Fabienne Vander Heiden, Matthew G. Vasseur, Sophie Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions |
| title | Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions |
| title_full | Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions |
| title_fullStr | Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions |
| title_full_unstemmed | Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions |
| title_short | Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions |
| title_sort | collagen derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions |
| url | http://hdl.handle.net/1721.1/113569 https://orcid.org/0000-0002-8607-1787 https://orcid.org/0000-0002-6702-4192 |
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