Reduced angiogenesis and tumor progression in gelatinase A-deficient mice.
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.
Itoh
T
T
Shionogi Institute for Medical Science, Shionogi & Co., Ltd., Osaka, Japan. takeshi.itoh@shionogi.co.jp
Tanioka
M
M
Yoshida
H
H
Yoshioka
T
T
Nishimoto
H
H
Itohara
S
S
D000818:Animals; D002455:Cell Division; D002465:Cell Movement / Q000235:genetics; D018093:Gelatinases / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008546:Melanoma, Experimental / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D008666:Metalloendopeptidases / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009389:Neovascularization, Pathologic / Q000235:genetics*
D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2