Experimental metastasis is suppressed in MMP-9-deficient mice |
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Authors: | Takeshi Itoh Masatoshi Tanioka Hidetoshi Matsuda Hirofumi Nishimoto Takayuki Yoshioka Ryuji Suzuki Masahiro Uehira |
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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 |
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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. |
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Keywords: | experimental tumor metastasis gelatinase knockout mice matrix metalloproteinase |
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