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Proteomic characterization of human multiple myeloma bone marrow

ABSTRACT: Glavey SV, Naba A, Manier S, Clauser KR, Tahri S, Park J, Reagan MR, Moschetta M, Mishima Y, Gambella M, Rocci A, Sacco A, Asara JM, Palumbo A, Roccaro AM, Hynes RO, Ghobrial IM. 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 to healthy donor-derived BM ECM. In this study, we show that the tumor ECM is remodeled at the mRNA and protein level 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

INSTRUMENT(S): LTQ Orbitrap XL, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: John Asara

PROVIDER: MSV000080451 | MassIVE | Fri Jan 06 08:22:00 GMT 2017

REPOSITORIES: MassIVE

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