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

Journal article

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.

Authors: Lwin, S; Fowler, J; Drake, M; Edwards, J; Lynch, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Verlag
• Journal: Molecular Cancer More from this journal
• Volume: 16
• Issue: 49
• Pages: 1-8
• Publication date: 2017-02-28
• Acceptance date: 2017-02-20
• DOI: 10.1186/s12943-017-0616-9
• ISSN: 1476-4598
• Language: English
• Keywords: Microenvironment; Mouse model; Osteoclast; Bone disease; MMP-7; Bone; Multiple myeloma