Matrix proteolysis is thought to play a crucial role in several stages of tumor progression, including angiogenesis, and the invasion and metastasis of tumor cells. We investigated the specific role of gelatinase A (matrix metalloproteinase 2) on these events using gelatinase A-deficient mice. In these mice, tumor-induced angiogenesis was suppressed according to dorsal air sac assay. When B16-BL6 melanoma cells or Lewis lung carcinoma cells were implanted intradermally, the tumor volumes at 3 weeks after implantation in the gelatinase A-deficient mice decreased by 39% for B16-BL6 melanoma and by 24% for Lewis lung carcinoma (P < 0.03 for each tumor). The number of lung colonies of i.v. injections fell by 54% for B16-BL6 melanoma and 77% for Lewis lung carcinoma (P < 0.014 and P < 0.0015, respectively). These results indicated that host-derived gelatinase A plays an important role in angiogenesis and tumor progression, suggesting the usefulness of gelatinase A inhibitors for anticancer chemotherapy.

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This work was partly supported by a Grant-in-Aid for Scientific Research B from the Ministry of Education, Science, Sports and Culture of Japan (to S. I.).

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