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

Molecular Cancer

Short Communication

J. A. Fowler¹  C. C. Lynch²  M. T. Drake³  J. R. Edwards⁴  C. M. Edwards⁵  S. T. Lwin⁵ 

[1] Department of Medicine/Clinical Pharmacology, Vanderbilt Center for Bone Biology, Nashville, USA;Department of Tumor Biology, H. Lee Moffitt Cancer Center, Tampa, FL, USA;Division of Endocrinology, Mayo Clinic College of Medicine, Rochester, MN, USA;Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Old Road, OX3 7LD, Oxford, UK;Department of Medicine/Clinical Pharmacology, Vanderbilt Center for Bone Biology, Nashville, USA;Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK;Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Old Road, OX3 7LD, Oxford, UK;Department of Medicine/Clinical Pharmacology, Vanderbilt Center for Bone Biology, Nashville, USA;

关键词: Multiple myeloma;    Bone;    MMP-7;    Osteoclast;    Microenvironment;    Bone disease;    Mouse model;   

DOI  :  10.1186/s12943-017-0616-9

 received in 2016-07-19, accepted in 2017-02-20,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2017