Transforming growth factor-beta suppresses the invasiveness of human fibrosarcoma cells in vitro by increasing expression of tissue inhibitor of metalloprotease

Biochem Biophys Res Commun. 1991 Apr 15;176(1):129-36. doi: 10.1016/0006-291x(91)90899-i.


We have investigated the effects of TGF-beta on the ability of the human fibrosarcoma cell line, HT1080, to invade a reconstituted basement membrane (Matrigel) in vitro. Exposure of HT1080 cells to TGF-beta (1-10ng/ml) caused a dose-dependent inhibition of HT1080 cell invasion. Unexpectedly, TGF-beta (10ng/ml) significantly enhanced (10-fold) the mRNA expression of the 68-72kDa latent type IV collagenase. Zymogram analysis revealed a 7-fold increase in the 68-72kDa latent type IV collagenase concomitant with an increase in the activated form (62kDa). TGF-beta induced the 92kDa type IV collagenase to a lesser degree. HT1080 cells exposed to TGF-beta also produced more tissue inhibitor of metalloprotease (TIMP) at both the mRNA (10-fold) and protein levels (5-fold). Although TGF-beta induced both type IV collagenases and TIMP, the net collagenolytic activity in the conditioned media after invasion assay was reduced in the presence of TGF-beta. The data suggest that the inhibition of invasiveness is due, at least in part, to the increased TIMP expression. These data suggest that TGF-beta may play a role in tumor cell invasion by increasing the expression of TIMP.

MeSH terms

  • Cell Line
  • Fibrosarcoma / pathology*
  • Gene Expression / drug effects
  • Glycoproteins / genetics*
  • Glycoproteins / pharmacology
  • Humans
  • Microbial Collagenase / antagonists & inhibitors
  • Microbial Collagenase / genetics*
  • Neoplasm Invasiveness
  • Nucleic Acid Hybridization
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • Recombinant Proteins / pharmacology
  • Tissue Inhibitor of Metalloproteinases
  • Transforming Growth Factor beta / pharmacology*


  • Glycoproteins
  • RNA, Messenger
  • Recombinant Proteins
  • Tissue Inhibitor of Metalloproteinases
  • Transforming Growth Factor beta
  • Microbial Collagenase