Article

Clinical & Experimental Metastasis

, Volume 17, Issue 2, pp 177-181

Experimental metastasis is suppressed in MMP-9-deficient mice

  • Takeshi ItohAffiliated withShionogi & Co., Ltd, Shionogi Institute for Medical Science
  • , Masatoshi TaniokaAffiliated withShionogi & Co., Ltd, Shionogi Institute for Medical Science
  • , Hidetoshi MatsudaAffiliated withShionogi & Co., Ltd, Shionogi Institute for Medical Science
  • , Hirofumi NishimotoAffiliated withShionogi & Co., Ltd, Shionogi Institute for Medical Science
  • , Takayuki YoshiokaAffiliated withDiscovery Research Laboratories, Shionogi & Co., Ltd
  • , Ryuji SuzukiAffiliated withShionogi & Co., Ltd, Shionogi Institute for Medical Science
  • , Masahiro UehiraAffiliated withShionogi & Co., Ltd, Shionogi Institute for Medical Science

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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.

experimental tumor metastasis gelatinase knockout mice matrix metalloproteinase