Serine proteinase activation in esophageal cancer

Anticancer Res. 2001 Jul-Aug;21(4A):2249-58.

Abstract

Background: Activation of the plasminogen/plasmin system seems to contribute to tumor aggressiveness and shorter post-operative survival. In the present study we examined the relation of uPA (urokinase plasminogen activator), uPAR (uPA receptor) and PAI-1 (plasminogen activator inhibitor type 1) to the biological growth behavior of esophageal cancer, as well as their influence on survival in esophageal cancer.

Materials and methods: The expression and distribution of uPA, uPAR and PAI-1 were analyzed by Northern blot analysis and immunostaining in 41 resected esophageal cancers and in normal esophagi.

Results: Northern blot analysis revealed a 5.0-, 3.6- and 5.4-fold increase in uPA, uPAR, and PAI-1 mRNA levels in esophageal cancer, respectively, in comparison to normal controls (p<0.01). These mRNA moieties were concomitantly increased in 86% of the tumors. uPA activity was 2.3-fold increased in esophageal cancer compared with normal controls (p<0.01). Statistical analysis revealed no differences in uPA, uPAR and PAI-1 immunoreactivity between well-differentiated, moderately-differentiated and poorly-differentiated tumors. Furthermore, survival analysis showed no difference in patients whose tumors exhibited positive uPA and uPAR immunostaining (median 11 months, range 4-36 months) versus patients whose tumors exhibited negative uPA and uPAR immunostaining (median 11 months, range 3-51 months).

Conclusion: Our data revealed that overexpression of uPA, uPAR and PAI-1 is often present in human esophageal carcinomas. However, up-regulation of these factors is not correlated with tumor differentiation or survival. These findings indicate that, unlike other tumors, uPA, uPAR and PAI-1 seem not to be prognostic markers for esophageal carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Northern
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / pathology
  • Enzyme Activation
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • Plasminogen Activator Inhibitor 1 / metabolism
  • RNA, Messenger / biosynthesis
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / metabolism
  • Receptors, Urokinase Plasminogen Activator
  • Urokinase-Type Plasminogen Activator / biosynthesis
  • Urokinase-Type Plasminogen Activator / metabolism*

Substances

  • PLAUR protein, human
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Urokinase-Type Plasminogen Activator