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Multiple Myeloma, Gammopathies

Proteomic characterization of human multiple myeloma bone marrow extracellular matrix

Leukemia volume 31, pages 2426–2434 (2017)Cite this article

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Abstract

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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Acknowledgements

This work was supported in part by NIH R01 CA181683-01A, R01 CA205954-01 and the Leukemia and Lymphoma Society to IMG, by the Health Research Board, Ireland, NSAFP, of which SVG is a recipient, and in part by the Howard Hughes Medical Institute, of which ROH is an investigator.

Author contributions

SVG, AN, SM, JP, ROH and IMG designed research. SVG, AN, SM, MRR, MM, YM, AS and JMA performed research. AR, MG and AP contributed clinical samples to this study. SVG, AN, SM, ST, JP, JMA, AMR and KC analyzed data. SVG, AN, SM, MEO’D, ROH and IMG wrote the paper.

Author information

Author notes

  1. A Naba, R O Hynes & I M Ghobrial

    Present address: 11Current address: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA.,

  2. S V Glavey, A Naba and S Manier: These authors contributed equally to this work.

  3. A M Roccaro: Co-last authors.

Authors and Affiliations

  1. Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    S V Glavey, S Manier, S Tahri, J Park, M R Reagan, M Moschetta, Y Mishima, A Sacco, A M Roccaro & I M Ghobrial

  2. Department of Hematology, National University of Ireland, Galway, Ireland

    S V Glavey & M E O'Dwyer

  3. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    A Naba & R O Hynes

  4. Protemics Platform, Broad Institute, Cambridge, MA, USA

    K Clauser

  5. University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy

    M Gambella & A Palumbo

  6. Manchester Royal Infirmary and Central Manchester University Hospital NHS Foundation, University of Manchester, Manchester, UK

    A Rocci

  7. Department Medical Oncology, SST Spedali Civili, CREA Laboratory, Brescia, Italy

    A Sacco & A M Roccaro

  8. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    J M Asara

  9. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA

    R O Hynes

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  1. S V Glavey
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Corresponding authors

Correspondence to R O Hynes or I M Ghobrial.

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Glavey, S., Naba, A., Manier, S. et al. Proteomic characterization of human multiple myeloma bone marrow extracellular matrix. Leukemia 31, 2426–2434 (2017). https://doi.org/10.1038/leu.2017.102

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