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Molecular Cancer
Published in: Molecular Cancer 1/2017

Open Access 01-12-2017 | Short communication

A loss of host-derived MMP-7 promotes myeloma growth and osteolytic bone disease in vivo

Authors: S. T. Lwin, J. A. Fowler, M. T. Drake, J. R. Edwards, C. C. Lynch, C. M. Edwards

Published in: Molecular Cancer | Issue 1/2017

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Abstract

Matrix metalloproteinases (MMPs) play a critical role in cancer pathogenesis, including tumor growth and osteolysis within the bone marrow microenvironment. However, the anti-tumor effects of MMPs are poorly understood, yet have significant implications for the therapeutic potential of targeting MMPs. Host derived MMP-7 has previously been shown to support the growth of bone metastatic breast and prostate cancer. In contrast and underscoring the complexity of MMP biology, here we identified a tumor-suppressive role for host MMP-7 in the progression of multiple myeloma in vivo. An increase in tumor burden and osteolytic bone disease was observed in myeloma-bearing MMP-7 deficient mice, as compared to wild-type controls. We observed that systemic MMP-7 activity was reduced in tumor-bearing mice and, in patients with multiple myeloma this reduced activity was concomitant with increased levels of the endogenous MMP inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1). Our studies have identified an unexpected tumour-suppressive role for host-derived MMP-7 in myeloma bone disease in vivo, and highlight the importance of elucidating the effect of individual MMPs in a disease-specific context.
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Metadata
Title
A loss of host-derived MMP-7 promotes myeloma growth and osteolytic bone disease in vivo
Authors
S. T. Lwin
J. A. Fowler
M. T. Drake
J. R. Edwards
C. C. Lynch
C. M. Edwards
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0616-9

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