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, 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.
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.|Department of Hematology, National University of Ireland, Galway, Ireland.
S V
SV
Glavey
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
A
A
Naba
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
S
S
Manier
Protemics Platform, Broad Institute, Cambridge, MA, USA.
K
K
Clauser
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
S
S
Tahri
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
J
J
Park
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
M R
MR
Reagan
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
M
M
Moschetta
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Y
Y
Mishima
University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
M
M
Gambella
Manchester Royal Infirmary and Central Manchester University Hospital NHS Foundation, University of Manchester, Manchester, UK.
A
A
Rocci
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.|SST Spedali Civili, Department Medical Oncology, CREA Laboratory, Brescia, Italy.
A
A
Sacco
Department of Hematology, National University of Ireland, Galway, Ireland.
M E
ME
O'Dwyer
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
J M
JM
Asara
University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
A
0000-0002-1763-6609
A
Palumbo
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.|SST Spedali Civili, Department Medical Oncology, CREA Laboratory, Brescia, Italy.
A M
AM
Roccaro
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
R O
RO
Hynes
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
I M
IM
Ghobrial
D017306:Annexin A2 / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism*; D016022:Case-Control Studies; D005109:Extracellular Matrix / Q000378:metabolism*; D037483:Galectin 1 / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020543:Proteome; D016019:Survival Analysis; D059016:Tumor Microenvironment
C472822:ANXA2 protein, human; D017306:Annexin A2; D037483:Galectin 1; C445499:LGALS1 protein, human; D020543:Proteome