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

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

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)49
Number of pages1
JournalMolecular cancer
Volume16
Issue number1
DOIs
StatePublished - Feb 28 2017

Keywords

  • Bone
  • Bone disease
  • MMP-7
  • Microenvironment
  • Mouse model
  • Multiple myeloma
  • Osteoclast

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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