Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells
<jats:title>Abstract</jats:title><jats:p>Pancreatic ductal adenocarcinoma (PDAC) has a collagen-rich dense extracellular matrix (ECM) that promotes malignancy of cancer cells and presents a barrier for drug delivery. Data analysis of our published mass spectrometry (MS)-based studi...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/136112 |
| _version_ | 1826200225076740096 |
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| author | Tian, Chenxi Huang, Ying Clauser, Karl R Rickelt, Steffen Lau, Allison N Carr, Steven A Vander Heiden, Matthew G Hynes, Richard O |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Tian, Chenxi Huang, Ying Clauser, Karl R Rickelt, Steffen Lau, Allison N Carr, Steven A Vander Heiden, Matthew G Hynes, Richard O |
| author_sort | Tian, Chenxi |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>Pancreatic ductal adenocarcinoma (PDAC) has a collagen-rich dense extracellular matrix (ECM) that promotes malignancy of cancer cells and presents a barrier for drug delivery. Data analysis of our published mass spectrometry (MS)-based studies on enriched ECM from samples of progressive PDAC stages reveal that the C-terminal prodomains of fibrillar collagens are partially uncleaved in PDAC ECM, suggesting reduced procollagen C-proteinase activity. We further show that the enzyme responsible for procollagen C-proteinase activity, bone morphogenetic protein1 (BMP1), selectively suppresses tumor growth and metastasis in cells expressing high levels of COL1A1. Although BMP1, as a secreted proteinase, promotes fibrillar collagen deposition from both cancer cells and stromal cells, only cancer-cell-derived procollagen cleavage and deposition suppresses tumor malignancy. These studies reveal a role for cancer-cell-derived fibrillar collagen in selectively restraining tumor growth and suggest stratification of patients based on their tumor epithelial collagen I expression when considering treatments related to perturbation of fibrillar collagens.</jats:p> |
| first_indexed | 2024-09-23T11:33:08Z |
| format | Article |
| id | mit-1721.1/136112 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:33:08Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1361122023-09-25T20:53:03Z Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells Tian, Chenxi Huang, Ying Clauser, Karl R Rickelt, Steffen Lau, Allison N Carr, Steven A Vander Heiden, Matthew G Hynes, Richard O Koch Institute for Integrative Cancer Research at MIT <jats:title>Abstract</jats:title><jats:p>Pancreatic ductal adenocarcinoma (PDAC) has a collagen-rich dense extracellular matrix (ECM) that promotes malignancy of cancer cells and presents a barrier for drug delivery. Data analysis of our published mass spectrometry (MS)-based studies on enriched ECM from samples of progressive PDAC stages reveal that the C-terminal prodomains of fibrillar collagens are partially uncleaved in PDAC ECM, suggesting reduced procollagen C-proteinase activity. We further show that the enzyme responsible for procollagen C-proteinase activity, bone morphogenetic protein1 (BMP1), selectively suppresses tumor growth and metastasis in cells expressing high levels of COL1A1. Although BMP1, as a secreted proteinase, promotes fibrillar collagen deposition from both cancer cells and stromal cells, only cancer-cell-derived procollagen cleavage and deposition suppresses tumor malignancy. These studies reveal a role for cancer-cell-derived fibrillar collagen in selectively restraining tumor growth and suggest stratification of patients based on their tumor epithelial collagen I expression when considering treatments related to perturbation of fibrillar collagens.</jats:p> 2021-10-27T20:30:51Z 2021-10-27T20:30:51Z 2021 2021-07-16T17:23:56Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136112 en 10.1038/s41467-021-22490-9 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Tian, Chenxi Huang, Ying Clauser, Karl R Rickelt, Steffen Lau, Allison N Carr, Steven A Vander Heiden, Matthew G Hynes, Richard O Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells |
| title | Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells |
| title_full | Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells |
| title_fullStr | Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells |
| title_full_unstemmed | Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells |
| title_short | Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells |
| title_sort | suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells |
| url | https://hdl.handle.net/1721.1/136112 |
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