Tumour cell thrombospondn-1 regulates tumour cell adhesion and invasion through the urokinase plasminogen activator receptor

D. Albo, V. L. Rothman, D. D. Roberts, G. P. Tuszynski

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

We have previously shown that platelet-produced thrombospondin-1 up-regulates the urokinase plasminogen activator and its receptor and promotes tumour cell invasion. Although tumour cells produce thrombospondin-1 in vivo, they produce only minimal amounts of thrombospondin-1 in vitro. To determine the effect of tumour cell-produced thrombospondin-1 in the regulation of the plasminogen/plasmin system and tumour cell invasion, we studied THBS-1-transfected MDA-MB-435 breast cancer cells that overexpress thrombospondin-1. The role of urokinase plasminogen receptor in thrombospondin-1-mediated adhesion and invasion was studied by antisense inhibition, enzymatic cleavage and antibody neutralization. Tumour cell adhesion to collagen and laminin was evaluated. Tumour cell invasion was studied in a modified Boyden chamber collagen invasion assay. Tumour cell thrombospondin-1 induced a 2-7 fold increase in urokinase plasminogen activator receptor and cell-associated urokinase plasminogen activator expression and a 50-65% increase in cell-associated urokinase plasminogen activator and plasmin activities. Furthermore, tumour cell thrombospondin-1 promoted tumour cell invasion and decreased tumour cell adhesion through up-regulation of urokinase plasminogen activator receptor-controlled urokinase plasminogen activator and plasmin activities. We conclude that tumour cell-produced thrombospondin-1 may play a critical role in the regulation of tumour cell adhesion and tumour cell invasion. (C) 2000 Cancer Research Campaign.

Original languageEnglish (US)
Pages (from-to)298-306
Number of pages9
JournalBritish Journal of Cancer
Volume83
Issue number3
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

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Keywords

  • Pericellular proteolysis
  • Plasmin
  • Urokinase plasminogen activator

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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