Experimental metastasis is suppressed in MMP-9-deficient mice.
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.
Shionogi Institute for Medical Science, Shionogi & Co., Ltd, Osaka, Japan. takeshi.itoh@shionogi.co.jp
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Itoh
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Tanioka
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Matsuda
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Nishimoto
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Yoshioka
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Suzuki
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Uehira
D000818:Animals; D017364:Collagenases / Q000172:deficiency / Q000502:physiology*; D005780:Gelatin / Q000032:analysis; D018093:Gelatinases / Q000378:metabolism; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000473:pathology* / Q000556:secondary*; D020780:Matrix Metalloproteinase 9; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology
D005780:Gelatin; D017364:Collagenases; D018093:Gelatinases; D020780:Matrix Metalloproteinase 9