Suppression of type I collagenase expression by antisense RNA in melanoma cells results in reduced synthesis of the urokinase-type plasminogen activator receptor

Biochem Biophys Res Commun. 1998 Jun 18;247(2):342-8. doi: 10.1006/bbrc.1998.8785.

Abstract

Previously we reported that suppression of type I collagenase synthesis in human melanoma cells with antisense RNA significantly reduced proteolysis of type I and type IV collagen matrices (Durko et al., 1997, Biochim. Biophys. Acta 1356, 271). Because plasmin is a major activator of the type I collagenase, we assessed the impact of type I collagenase suppression on the urokinase/plasmin system of proteolysis. Gel zymography revealed the appearance of two new caseinolytic bands of Mr 81-83000 in conditioned media of type I collagenase-depleted, but not of wild-type cells and these were identified as plasmin bands. This increased extracellular plasmin activity coincided with reduced membrane-associated plasminogen levels and decreased expression of the urokinase-type plasminogen activator receptor at both the mRNA (up to 83% reduction) and cell-surface (up to 48% reduction) levels, while urokinase mRNA levels remained unchanged. The results indicate that in these cells the urokinase/plasmin system is regulated by type I collagenase levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Collagenases / genetics*
  • Culture Media, Conditioned
  • Fibrinolysin / metabolism
  • Gene Expression / drug effects
  • Humans
  • Matrix Metalloproteinase 1
  • Melanoma / genetics*
  • Melanoma / metabolism*
  • Plasminogen Activators / metabolism
  • RNA, Antisense / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / genetics
  • Receptors, Urokinase Plasminogen Activator
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / genetics
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • Culture Media, Conditioned
  • PLAUR protein, human
  • RNA, Antisense
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Plasminogen Activators
  • Fibrinolysin
  • Urokinase-Type Plasminogen Activator
  • Collagenases
  • Matrix Metalloproteinase 1