REDUCED ANGIOGENESIS AND TUMOR PROGRESSION IN GELATINASE A-DEFICIENT MICE

Matrix proteolysis is thought to play a crucial role in several stages oi tumor progression, including angiogenesis, and the invasion and me tastasis of tumor cells, We investigated the specific role of gelatina se A (matrix metalloproteinase 2) on these events using gelatinase A-d eficient mice, In these mice, tumor-induced angiogenesis was suppresse d according to dorsal air sec assay. When B16-BL6 melanoma cells or Le wis lung carcinoma cells were implanted intradermally, the tumor volum es at 3 weeks after implantation in the gelatinase A-deficient mice de creased bg 39% far B16-BL6 melanoma and by 24% for Lewis lung carcinom a (P < 0.03 for each tumor), The number of lung colonies of i.v. injec tions fell by 54% for B16-BL6 melanoma and 77% for Lewis lung carcinom a (P < 0.014 and P < 0.0015, respectively). These results indicated th at host-derived gelatinase A plays an important role in angiogenesis a nd tumor progression, suggesting the usefulness of gelatinase A inhibi tors for anticancer chemotherapy.