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Proteomic characterization of human multiple myeloma bone marrow extracellular matrix.

Leukemia. 2017 Nov;31(11):2426-2434. Epub 2017 Mar 27
S V Glavey 1 , A Naba 2 , S Manier 3 , K Clauser 4 , S Tahri 3 , J Park 3 , M R Reagan 3 , M Moschetta 3 , Y Mishima 3 , M Gambella 5 , A Rocci 6 , A Sacco 7 , M E O'Dwyer 1 , J M Asara 8 , A Palumbo 5 , A M Roccaro 7 , R O Hynes 9 , I M Ghobrial 3
S V Glavey 1 , A Naba 2 , S Manier 3 , K Clauser 4 , S Tahri 3 , J Park 3 , M R Reagan 3 , M Moschetta 3 , Y Mishima 3 , M Gambella 5 , A Rocci 6 , A Sacco 7 , M E O'Dwyer 1 , J M Asara 8 , A Palumbo 5 , A M Roccaro 7 , R O Hynes 9 , I M Ghobrial 3
+ et al

[No authors listed]

Author information
  • 1 Department of Hematology, National University of Ireland, Galway, Ireland.
  • 2 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 3 Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • 4 Protemics Platform, Broad Institute, Cambridge, MA, USA.
  • 5 University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
  • 6 Manchester Royal Infirmary and Central Manchester University Hospital NHS Foundation, University of Manchester, Manchester, UK.
  • 7 SST Spedali Civili, Department Medical Oncology, CREA Laboratory, Brescia, Italy.
  • 8 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • 9 Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.

摘要

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.

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