January 8, 2015

Enzyme affects tumor metastasis

A protein that degrades the “matrix” between cells participates in the development of lung metastases from primary breast cancer in mouse models and may be a good target for breast cancer treatment.

by Daren Diiorio

Breast cancer remains the most common type of cancer in females, with survival rates decreasing sharply for those with distant metastases. MMP2, a type of enzyme that degrades the extracellular matrix, has previously been implicated in the development of distant tumor metastases, but without a clearly defined role.

In the Journal of Pathology, Barbara Fingleton, Ph.D., and colleagues establish a role for MMP2 in the development of lung metastases from primary breast cancer. Using mice without the Mmp2 gene, the team found that metastatic tumors in the lung proliferate less in the absence of fibroblast MMP2.

The researchers showed that one function of MMP2 in lung metastasis is the regulation of fibroblast activation and collagen expression. They suggest that MMP2 generates active TGFbeta-1, and showed that supplying active TGFbeta-1 restores collagen expression in Mmp2-deficient fibroblasts.

The results indicate that selective MMP2 inhibitors may serve as potential pharmacologic agents for breast cancer treatment.

This research was supported by grants from the National Institutes of Health (CA084360, CA163072, GM062459, CA119925).

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