Decreased expression of tissue inhibitor of metalloproteinases in metastatic tumor cells leading to increased levels of collagenase activity

Cancer Res. 1991 Apr 15;51(8):2138-43.


We have examined the expression of murine tissue inhibitor of metalloproteinases (TIMP) in nonmetastatic and metastatic cell lines derived from SP1 murine mammary adenocarcinoma cells. We observed decreased levels of TIMP mRNA and activity in metastatic cells as compared to their nonmetastatic equivalents in the absence of fetal bovine serum. Lower levels of TIMP mRNA correlated to decreased levels of transcription of the TIMP gene. Net collagenase activity was higher in metastatic cells, but metastatic and nonmetastatic cells secreted similar levels of total collagenase (mainly type IV). This suggests that decreased TIMP gene expression results in increased net collagenase activity in malignant cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Culture Media / chemistry
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Mammary Neoplasms, Animal / enzymology*
  • Mammary Neoplasms, Animal / genetics
  • Metalloendopeptidases / antagonists & inhibitors*
  • Microbial Collagenase / metabolism*
  • Neoplasm Metastasis
  • RNA, Messenger / analysis*
  • RNA, Neoplasm / analysis*
  • Tissue Inhibitor of Metalloproteinases


  • Culture Media
  • Glycoproteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Tissue Inhibitor of Metalloproteinases
  • Metalloendopeptidases
  • Microbial Collagenase