Thrombospondin (TSP) and Transforming Growth Factor β 1 (TGF-β) Promote Human A549 Lung Carcinoma Cell Plasminogen Activator Inhibitor Type 1 (Pal-1) Production and Stimulate Tumor Cell Attachment in Vitro

D. Albo, J. P. Arnoletti, A. Castiglioni, M. S. Granick, M. P. Solomon, V. L. Rothman, G. P. Tuszynski

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46 Scopus citations

Abstract

A growing body of evidence has recently implicated TSP and TGF-β in the process of malignancy, such as tumor cell proliferation, tumor angiogenesis, and metastasis. The purpose of the present study was to evaluate potential mechanisms of TSP and TGF-β in tumor cell attachment and invasion. Our results indicate that both TSP and TGF-β promoted tumor cell attachment and spreading in the presence of plasminogen. The mechanism for these effects appeared to be due, in part, to the capacity of TSP and TGF-β to induce tumor cell production of (PAI-1). PAI-1, which is a natural inhibitor of tumor-cell associated urokinase-type plasminogen activator (uPA) activity, inhibited activation of plasminogen to plasmin in the growth media,thereby preventing plasmin-induced detachment of cells. The TSP-promoted production of PAI-1 could be inhibited not only by anti-TSP antibodies but also by a neutralizing antibody against TGF-β. These results suggest that TSP by a mechanism involving TGF-β can promote cell adhesion through stimulation of tumor cell secretion of PAI-1. These data provide evidence that TSP not only has the capacity of functioning as a matrix protein to directly promote cell-substratum adhesion but that TSP can also stimulate cell adhesion and spreading by modulating cell surface protease expression through stimulation of tumor-associated production of PAI-1.

Original languageEnglish (US)
Pages (from-to)857-865
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume203
Issue number2
DOIs
Publication statusPublished - Sep 15 1994
Externally publishedYes

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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