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Experimental metastasis is suppressed in MMP-9-deficient mice
Authors:Takeshi Itoh  Masatoshi Tanioka  Hidetoshi Matsuda  Hirofumi Nishimoto  Takayuki Yoshioka  Ryuji Suzuki  Masahiro Uehira
Affiliation:(1) Shionogi & Co., Ltd, Shionogi Institute for Medical Science, Japan;(2) Discovery Research Laboratories, Shionogi & Co., Ltd, 12-4, Sagisu 5-chome, Fukushima-ku, Osaka, 553-0002, Japan
Abstract:Matrix metalloproteinases (MMPs) are thought to play a key role in tumor invasion and metastasis. The role of MMP-9 (gelatinase B) in tumor metastasis was examined in MMP-9-deficient mice produced by gene targeting using embryonic stem cells. MMP-9-deficient mice develop normally and are fertile. In these mice, the number of metastatic colonies of B16-BL6 melanoma cells or Lewis lung carcinoma cells that were implanted intravenously fell by 45% for B16-BL6 melanoma and 59% for Lewis lung carcinoma (p=0.03 and p=0.0043, respectively). Gelatin zymography showed that both tumor cell lines did not secrete MMP-9 by themselves but the host cells surrounding the tumor cells secrete MMP-9 in vivo. These results indicated that host-derived MMP-9 plays an important role in the process of tumor metastasis.
Keywords:experimental tumor metastasis  gelatinase  knockout mice  matrix metalloproteinase
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