Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma
© Lau et al. Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to iso...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications, Ltd
2021
|
| Online Access: | https://hdl.handle.net/1721.1/135492 |
| _version_ | 1826197970291261440 |
|---|---|
| author | Lau, Allison N Li, Zhaoqi Danai, Laura V Westermark, Anna M Darnell, Alicia M Ferreira, Raphael Gocheva, Vasilena Sivanand, Sharanya Lien, Evan C Sapp, Kiera M Mayers, Jared R Biffi, Giulia Chin, Christopher R Davidson, Shawn M Tuveson, David A Jacks, Tyler Matheson, Nicholas J Yilmaz, Omer Vander Heiden, Matthew G |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Lau, Allison N Li, Zhaoqi Danai, Laura V Westermark, Anna M Darnell, Alicia M Ferreira, Raphael Gocheva, Vasilena Sivanand, Sharanya Lien, Evan C Sapp, Kiera M Mayers, Jared R Biffi, Giulia Chin, Christopher R Davidson, Shawn M Tuveson, David A Jacks, Tyler Matheson, Nicholas J Yilmaz, Omer Vander Heiden, Matthew G |
| author_sort | Lau, Allison N |
| collection | MIT |
| description | © Lau et al. Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells. To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used to assess differences between cancer cell and fibroblast metabolism in murine pancreatic cancer organoid- fibroblast co-cultures and tumors. Pancreatic cancer cells exhibited increased pyruvate carboxylation relative to fibroblasts, and this flux depended on both pyruvate carboxylase and malic enzyme 1 activity. Consequently, expression of both enzymes in cancer cells was necessary for organoid and tumor growth, demonstrating that dissecting the metabolism of specific cell populations within heterogeneous systems can identify dependencies that may not be evident from studying isolated cells in culture or bulk tissue. |
| first_indexed | 2024-09-23T10:56:37Z |
| format | Article |
| id | mit-1721.1/135492 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:56:37Z |
| publishDate | 2021 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| spelling | mit-1721.1/1354922023-12-22T21:06:19Z Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma Lau, Allison N Li, Zhaoqi Danai, Laura V Westermark, Anna M Darnell, Alicia M Ferreira, Raphael Gocheva, Vasilena Sivanand, Sharanya Lien, Evan C Sapp, Kiera M Mayers, Jared R Biffi, Giulia Chin, Christopher R Davidson, Shawn M Tuveson, David A Jacks, Tyler Matheson, Nicholas J Yilmaz, Omer Vander Heiden, Matthew G Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Biology © Lau et al. Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells. To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used to assess differences between cancer cell and fibroblast metabolism in murine pancreatic cancer organoid- fibroblast co-cultures and tumors. Pancreatic cancer cells exhibited increased pyruvate carboxylation relative to fibroblasts, and this flux depended on both pyruvate carboxylase and malic enzyme 1 activity. Consequently, expression of both enzymes in cancer cells was necessary for organoid and tumor growth, demonstrating that dissecting the metabolism of specific cell populations within heterogeneous systems can identify dependencies that may not be evident from studying isolated cells in culture or bulk tissue. 2021-10-27T20:23:41Z 2021-10-27T20:23:41Z 2020 2021-07-16T18:18:18Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135492 en 10.7554/ELIFE.56782 eLife Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd eLife |
| spellingShingle | Lau, Allison N Li, Zhaoqi Danai, Laura V Westermark, Anna M Darnell, Alicia M Ferreira, Raphael Gocheva, Vasilena Sivanand, Sharanya Lien, Evan C Sapp, Kiera M Mayers, Jared R Biffi, Giulia Chin, Christopher R Davidson, Shawn M Tuveson, David A Jacks, Tyler Matheson, Nicholas J Yilmaz, Omer Vander Heiden, Matthew G Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma |
| title | Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma |
| title_full | Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma |
| title_fullStr | Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma |
| title_full_unstemmed | Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma |
| title_short | Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma |
| title_sort | dissecting cell type specific metabolism in pancreatic ductal adenocarcinoma |
| url | https://hdl.handle.net/1721.1/135492 |
| work_keys_str_mv | AT lauallisonn dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT lizhaoqi dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT danailaurav dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT westermarkannam dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT darnellaliciam dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT ferreiraraphael dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT gochevavasilena dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT sivanandsharanya dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT lienevanc dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT sappkieram dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT mayersjaredr dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT biffigiulia dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT chinchristopherr dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT davidsonshawnm dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT tuvesondavida dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT jackstyler dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT mathesonnicholasj dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT yilmazomer dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma AT vanderheidenmatthewg dissectingcelltypespecificmetabolisminpancreaticductaladenocarcinoma |