Transformation of epithelial Madin-Darby canine kidney cells with p60(v-src) induces expression of membrane-type 1 matrix metalloproteinase and invasiveness

Cancer Res. 1998 May 15;58(10):2240-4.


Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed both in carcinoma cells and in surrounding stromal fibroblasts. MT1-MMP localizes to the surface of tumor cells and is thought to play an important role in tumor invasion. To analyze the mechanism of MT1-MMP gene expression in epithelial tumor cells, the dog kidney epithelial cell line Madin-Darby canine kidney (MDCK) was transformed by oncogenes, including v-src, and expression of MT1-MMP was examined. Transformation of MDCK cells with v-src resulted in loss of cell-to-cell contacts and morphological change. Expression of MT1-MMP in v-src-transformed cells was identified by Northern and Western blotting. Gelatin zymography analysis showed that progelatinase A in the culture medium was processed from latent to activated form by MDCK cells transformed with v-src. The MDCK cells transformed by v-src were tumorigenic in the subcutis (ectopic) and kidney (orthotopic) of nude mice and spontaneously metastasized to the lung after orthotopic implantation. These results suggest that MT1-MMP induced by v-src transformation may promote invasiveness of transformed cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Transformation, Neoplastic / genetics*
  • Dogs
  • Enzyme Induction
  • Epithelial Cells / pathology
  • Matrix Metalloproteinase 14
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / biosynthesis*
  • Metalloendopeptidases / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis*
  • Oncogene Protein pp60(v-src) / genetics*
  • Transfection


  • Mmp14 protein, mouse
  • Neoplasm Proteins
  • Oncogene Protein pp60(v-src)
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 14