Proteomic characterization of human multiple myeloma bone marrow extracellular matrix
The extracellular matrix (ECM) is a major component of the tumor microenvironment, contributing to the regulation of cell survival, proliferation, differentiation and metastasis. In multiple myeloma (MM), interactions between MM cells and the bone marrow (BM) microenvironment, including the BM ECM,...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/117210 https://orcid.org/0000-0001-7603-8396 |
| _version_ | 1811085351395000320 |
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| author | Glavey, S V Manier, S Clauser, K Tahri, S Park, J Reagan, M R Moschetta, M Mishima, Y Gambella, M Rocci, A Sacco, A O'Dwyer, M E Asara, J M Palumbo, A Roccaro, A M Ghobrial, I M Naba, Alexandra Hynes, Richard O |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Glavey, S V Manier, S Clauser, K Tahri, S Park, J Reagan, M R Moschetta, M Mishima, Y Gambella, M Rocci, A Sacco, A O'Dwyer, M E Asara, J M Palumbo, A Roccaro, A M Ghobrial, I M Naba, Alexandra Hynes, Richard O |
| author_sort | Glavey, S V |
| collection | MIT |
| description | The extracellular matrix (ECM) is a major component of the tumor microenvironment, contributing to the regulation of cell survival, proliferation, differentiation and metastasis. In multiple myeloma (MM), interactions between MM cells and the bone marrow (BM) microenvironment, including the BM ECM, are critical to the pathogenesis of the disease and the development of drug resistance. Nevertheless, composition of the ECM in MM and its role in supporting MM pathogenesis has not been reported. We have applied a novel proteomic-based strategy and defined the BM ECM composition in patients with monoclonal gammopathy of undetermined significance (MGUS), newly diagnosed and relapsed MM compared with healthy donor-derived BM ECM. In this study, we show that the tumor ECM is remodeled at the mRNA and protein levels in MGUS and MM to allow development of a permissive microenvironment. We further demonstrate that two ECM-affiliated proteins, ANXA2 and LGALS1, are more abundant in MM and high expression is associated with a decreased overall survival. This study points to the importance of ECM remodeling in MM and provides a novel proteomic pipeline for interrogating the role of the ECM in cancers with BM tropism. |
| first_indexed | 2024-09-23T13:08:14Z |
| format | Article |
| id | mit-1721.1/117210 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:08:14Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1172102022-09-28T12:11:34Z Proteomic characterization of human multiple myeloma bone marrow extracellular matrix Glavey, S V Manier, S Clauser, K Tahri, S Park, J Reagan, M R Moschetta, M Mishima, Y Gambella, M Rocci, A Sacco, A O'Dwyer, M E Asara, J M Palumbo, A Roccaro, A M Ghobrial, I M Naba, Alexandra Hynes, Richard O Koch Institute for Integrative Cancer Research at MIT Hynes Richard Naba, Alexandra Hynes, Richard O The extracellular matrix (ECM) is a major component of the tumor microenvironment, contributing to the regulation of cell survival, proliferation, differentiation and metastasis. In multiple myeloma (MM), interactions between MM cells and the bone marrow (BM) microenvironment, including the BM ECM, are critical to the pathogenesis of the disease and the development of drug resistance. Nevertheless, composition of the ECM in MM and its role in supporting MM pathogenesis has not been reported. We have applied a novel proteomic-based strategy and defined the BM ECM composition in patients with monoclonal gammopathy of undetermined significance (MGUS), newly diagnosed and relapsed MM compared with healthy donor-derived BM ECM. In this study, we show that the tumor ECM is remodeled at the mRNA and protein levels in MGUS and MM to allow development of a permissive microenvironment. We further demonstrate that two ECM-affiliated proteins, ANXA2 and LGALS1, are more abundant in MM and high expression is associated with a decreased overall survival. This study points to the importance of ECM remodeling in MM and provides a novel proteomic pipeline for interrogating the role of the ECM in cancers with BM tropism. 2018-07-31T13:14:28Z 2018-07-31T13:14:28Z 2017-03 2016-12 Article http://purl.org/eprint/type/JournalArticle 0887-6924 1476-5551 http://hdl.handle.net/1721.1/117210 Glavey, S. V. et al. “Proteomic Characterization of Human Multiple Myeloma Bone Marrow Extracellular Matrix.” Leukemia 31, 11 (March 2017): 2426–2434 https://orcid.org/0000-0001-7603-8396 en_US https://doi.org/10.1038/leu.2017.102 Leukemia Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group Prof. Hynes via Courtney Crummett |
| spellingShingle | Glavey, S V Manier, S Clauser, K Tahri, S Park, J Reagan, M R Moschetta, M Mishima, Y Gambella, M Rocci, A Sacco, A O'Dwyer, M E Asara, J M Palumbo, A Roccaro, A M Ghobrial, I M Naba, Alexandra Hynes, Richard O Proteomic characterization of human multiple myeloma bone marrow extracellular matrix |
| title | Proteomic characterization of human multiple myeloma bone marrow extracellular matrix |
| title_full | Proteomic characterization of human multiple myeloma bone marrow extracellular matrix |
| title_fullStr | Proteomic characterization of human multiple myeloma bone marrow extracellular matrix |
| title_full_unstemmed | Proteomic characterization of human multiple myeloma bone marrow extracellular matrix |
| title_short | Proteomic characterization of human multiple myeloma bone marrow extracellular matrix |
| title_sort | proteomic characterization of human multiple myeloma bone marrow extracellular matrix |
| url | http://hdl.handle.net/1721.1/117210 https://orcid.org/0000-0001-7603-8396 |
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