Preclinical Study

Breast Cancer Research and Treatment

, Volume 116, Issue 1, pp 79-90

First online:

Matrix metalloproteinase-1 promotes breast cancer angiogenesis and osteolysis in a novel in vivo model

  • S. M. EckAffiliated withDepartment of Biochemistry, Dartmouth Medical School
  • , P. J. HoopesAffiliated withThayer School of Engineering, Dartmouth College
  • , B. L. PetrellaAffiliated withDepartment of Medicine, Norris Cotton Cancer Center
  • , C. I. CoonAffiliated withDepartment of Medicine, Norris Cotton Cancer Center
  • , C. E. BrinckerhoffAffiliated withDepartment of Biochemistry, Dartmouth Medical SchoolDepartment of Medicine, Norris Cotton Cancer Center Email author 

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Matrix metalloproteinase-1 (MMP-1) is critical for mediating breast cancer metastasis to bone. We investigated the role of MMP-1 in breast cancer invasion of soft tissues and bone using human MDA MB-231 breast cancer cells stably transfected with shRNAs against MMP-1 and a novel murine model of bone invasion. MMP-1 produced by breast cancer cells with control shRNA facilitated invasion of tumors into soft tissue in vivo, which correlated with enhanced blood vessel formation at the invasive edge, compared to tumors with silenced MMP-1 expression. Tumors expressing MMP-1 were also associated with osteolysis in vivo, whereas tumors with inhibited MMP-1 levels were not. Additionally, tumor-secreted MMP-1 activated bone-resorbing osteoclasts in vitro. Together, these data suggest a mechanism for MMP-1 in the activation of osteoclasts in vivo. We conclude that breast cancer-derived MMP-1 mediates invasion through soft tissues and bone via mechanisms involving matrix degradation, angiogenesis, and osteoclast activation.


Breast cancer Bone Invasion Metastasis MMP Murine model