Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters
The extracellular matrix (ECM) is a major component of tumors and a significant contributor to cancer progression. In this study, we use proteomics to investigate the ECM of human mammary carcinoma xenografts and show that primary tumors of differing metastatic potential differ in ECM composition. B...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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eLife Sciences Publications, Ltd.
2014
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| Online Access: | http://hdl.handle.net/1721.1/89181 https://orcid.org/0000-0001-7603-8396 |
| _version_ | 1826190067307118592 |
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| author | Naba, Alexandra Clauser, Karl R. Carr, Steven A. Lamar, John Hynes, Richard O |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Naba, Alexandra Clauser, Karl R. Carr, Steven A. Lamar, John Hynes, Richard O |
| author_sort | Naba, Alexandra |
| collection | MIT |
| description | The extracellular matrix (ECM) is a major component of tumors and a significant contributor to cancer progression. In this study, we use proteomics to investigate the ECM of human mammary carcinoma xenografts and show that primary tumors of differing metastatic potential differ in ECM composition. Both tumor cells and stromal cells contribute to the tumor matrix and tumors of differing metastatic ability differ in both tumor- and stroma-derived ECM components. We define ECM signatures of poorly and highly metastatic mammary carcinomas and these signatures reveal up-regulation of signaling pathways including TGFβ and VEGF. We further demonstrate that several proteins characteristic of highly metastatic tumors (LTBP3, SNED1, EGLN1, and S100A2) play causal roles in metastasis, albeit at different steps. Finally we show that high expression of LTBP3 and SNED1 correlates with poor outcome for ER−/PR−breast cancer patients. This study thus identifies novel biomarkers that may serve as prognostic and diagnostic tools. |
| first_indexed | 2024-09-23T08:34:32Z |
| format | Article |
| id | mit-1721.1/89181 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:34:32Z |
| publishDate | 2014 |
| publisher | eLife Sciences Publications, Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/891812022-09-30T09:40:52Z Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters Naba, Alexandra Clauser, Karl R. Carr, Steven A. Lamar, John Hynes, Richard O Koch Institute for Integrative Cancer Research at MIT Naba, Alexandra Lamar, John Michael Hynes, Richard O. The extracellular matrix (ECM) is a major component of tumors and a significant contributor to cancer progression. In this study, we use proteomics to investigate the ECM of human mammary carcinoma xenografts and show that primary tumors of differing metastatic potential differ in ECM composition. Both tumor cells and stromal cells contribute to the tumor matrix and tumors of differing metastatic ability differ in both tumor- and stroma-derived ECM components. We define ECM signatures of poorly and highly metastatic mammary carcinomas and these signatures reveal up-regulation of signaling pathways including TGFβ and VEGF. We further demonstrate that several proteins characteristic of highly metastatic tumors (LTBP3, SNED1, EGLN1, and S100A2) play causal roles in metastasis, albeit at different steps. Finally we show that high expression of LTBP3 and SNED1 correlates with poor outcome for ER−/PR−breast cancer patients. This study thus identifies novel biomarkers that may serve as prognostic and diagnostic tools. National Cancer Institute (U.S.) (Tumor Microenvironment Network, grant no. U54 CA126515/CA163109) National Cancer Institute (U.S.) (David H. Koch Institute Support Grant P30-CA14051) Howard Hughes Medical Institute Broad Institute of MIT and Harvard National Institutes of Health (U.S.) (NIH/National Research and Service Award) Virginia and D. K. Ludwig Fund for Cancer Research National Cancer Center 2014-09-04T19:56:42Z 2014-09-04T19:56:42Z 2014-03 2013-07 Article http://purl.org/eprint/type/JournalArticle 2050-084X http://hdl.handle.net/1721.1/89181 Naba, Alexandra, Karl R Clauser, John M Lamar, Steven A Carr, and Richard O Hynes. “Extracellular Matrix Signatures of Human Mammary Carcinoma Identify Novel Metastasis Promoters.” eLife 2014;3:e01308 (March 11, 2014). https://orcid.org/0000-0001-7603-8396 en_US http://dx.doi.org/10.7554/eLife.01308 eLife Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf eLife Sciences Publications, Ltd. eLife Sciences Publications, Ltd. |
| spellingShingle | Naba, Alexandra Clauser, Karl R. Carr, Steven A. Lamar, John Hynes, Richard O Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters |
| title | Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters |
| title_full | Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters |
| title_fullStr | Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters |
| title_full_unstemmed | Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters |
| title_short | Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters |
| title_sort | extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters |
| url | http://hdl.handle.net/1721.1/89181 https://orcid.org/0000-0001-7603-8396 |
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