Expression of membrane-type matrix metalloproteinase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay

Cancer Res. 1996 Dec 15;56(24):5678-83.

Abstract

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a member of the recently identified unique membrane-type subgroup in the matrix metalloproteinase (MMP) family. MT1-MMP has proteolytic activity against components in the extracellular matrix and activates progelatinase A (72-kDa type IV procollagenase/proMMP-2) on the cell surface. Because MT1-MMP is frequently expressed in a variety of tumors, we examined its contribution to their metastatic potential. The mouse lung carcinoma cell line Madison 109 was transiently transfected with a MT1-MMP expression plasmid and inoculated into the tail vein of BALB/c mouse. Fate of the transfected cells was monitored by the neo(r) gene in the plasmid using the quantitative PCR method. The survival rate of the parental cells in lung was 0.7% of the inoculated cells. It was increased by 3-fold with the MT1-MMP transfected cells and the number of the lung nodules increased accordingly. Immunostaining of the consecutive tissue sections revealed that lung nodules expressing MT1-MMP were positive for gelatinase A as well, whereas MT1-MMP-negative cells were not stained for gelatinase A at all. Thus, MT1-MMP-expressing cells acquire specific ability to bind exogenous progelatinase A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antisense Elements (Genetics) / genetics
  • Cell Adhesion
  • Fibrosarcoma / enzymology
  • Gelatinases / genetics
  • Gelatinases / metabolism*
  • Gene Expression
  • Genetic Vectors
  • Humans
  • Lung Neoplasms / secondary*
  • Matrix Metalloproteinase 14
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mice
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antisense Elements (Genetics)
  • Mmp14 protein, mouse
  • Neoplasm Proteins
  • Gelatinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 14