Eck SM et al. - Breast cancer-derived MMP-1 mediates invasion through soft tissues and bone via mechanisms involving matrix degradation, angiogenesis, and osteoclast activation. Methods
Study to investigate the role of MMP-1 in BCa invasion of soft tissues and bone
Human MDA MB-231 breast cancer cells stably transfected with shRNAs against MMP-1
A novel murine model of bone invasion was used
Results
MMP-1 produced by BCa cells with control shRNA facilitated invasion of tumors into soft tissue in vivo
This correlated with enhanced blood vessel formation at the invasive edge vs tumors with silenced MMP-1 expression
Tumors expressing MMP-1 were also associated with osteolysis in vivo vs tumors with inhibited MMP-1 levels
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
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