Thrombospondin-1 and Transforming Growth Factor Beta-1 Upregulate Plasminogen Activator Inhibitor Type 1 in Pancreatic Cancer

Daniel Albo, David H. Berger, Jon Vogel, George P. Tuszynski

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Controlled degradation of the extracellular matrix by proteases is crucial in tumor cell invasion. We have shown that thrombospondin-1 (TSP-1), through activation of transforming growth factor beta-1 (TGF-β1), regulates the plasminogen/plasmin protease system in breast cancer. To determine whether this occurred in other epithelial neoplasms, we studied the role of TSP-1 and TGF-β1 in the regulation of the plasminogen/plasmin system in pancreatic cancer. ASPC-1 and COLO-357 pancreatic cancer cells were treated with TSP-1 or TGF-β1 at varying concentrations. The TSP-1 and TGF-β1-treated cells were also treated with either anti-TSP-1, anti-TSP-1 receptor, or anti-TGF-β1 antibodies. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression was determined by enzyme-linked immunosorbent assay. TSP-1 and TGF-β1 promoted a dose-dependent upregulation of ASPC-1 and COLO-357 PAI-1 expression. The TSP-1 effect could be blocked with anti-TSP-1 or anti-TGF-β1 antibodies. The TGF-β1 effect could be blocked only with anti-TGF-β1 antibody. Anti-TSP-1 receptor antibody blocked the TSP-1 effect on PAI-1 expression but had no effect on TGF-β1-mediated PAI-1 expression. Neither TSP-1 nor TGF-β1 had an effect on uPA production. We conclude that TSP-1, in a receptor-mediated process that involves the activation of TGF-β1, upregulates PAI-1 expression in pancreatic cancer without an effect on uPA production.

Original languageEnglish (US)
Pages (from-to)411-417
Number of pages7
JournalJournal of Gastrointestinal Surgery
Volume3
Issue number4
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Keywords

  • Pancreatic neoplasms
  • Plasminogen activator inhibitor
  • Thrombospondin-1
  • Transforming growth factor beta-1
  • Urokinase plasminogen activator

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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