Experimental Metastasis Is Suppressed in MMP-9-deficient Mice

Clin Exp Metastasis. 1999 Mar;17(2):177-81. doi: 10.1023/a:1006603723759.

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.

MeSH terms

  • Animals
  • Collagenases / deficiency
  • Collagenases / physiology*
  • Gelatin / analysis
  • Gelatinases / metabolism
  • Infusions, Intravenous
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / secondary*
  • Matrix Metalloproteinase 9
  • Melanoma, Experimental / pathology*
  • Mice
  • Mice, Knockout
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / physiology

Substances

  • Gelatin
  • Collagenases
  • Gelatinases
  • Matrix Metalloproteinase 9