Thrombospondin (TSP) and transforming growth factor beta 1 (TGF-beta) promote human A549 lung carcinoma cell plasminogen activator inhibitor type 1 (PAI-1) production and stimulate tumor cell attachment in vitro
| Autor: | M.P. Solomon, G.P. Tuszynski, A. Castiglioni, V. L. Rothman, D. Albo, J. P. Arnoletti, M.S. Granick |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
endocrine system
Lung Neoplasms Plasmin Cell Biophysics Biology Adenocarcinoma Biochemistry Antibodies immune system diseases Transforming Growth Factor beta Plasminogen Activator Inhibitor 1 medicine Cell Adhesion Tumor Cells Cultured Humans Secretion Fibrinolysin Cell adhesion Neutralizing antibody Molecular Biology Thrombospondin Membrane Glycoproteins virus diseases Cell Biology Molecular biology Urokinase-Type Plasminogen Activator medicine.anatomical_structure biology.protein Cancer research Thrombospondins Plasminogen activator medicine.drug Transforming growth factor |
| Zdroj: | Biochemical and biophysical research communications. 203(2) |
| ISSN: | 0006-291X |
| Popis: | A growing body of evidence has recently implicated TSP and TGF-beta 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-beta in tumor cell attachment and invasion. Our results indicate that both TSP and TGF-beta 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-beta 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-beta. These results suggest that TSP by a mechanism involving TGF-beta 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|