THROMBOSPONDIN-1 AND TRANSFORMING GROWTH FACTOR-BETA1 PROMOTE BREAST-TUMOR CELL INVASION THROUGH UP-REGULATION OF THE PLASMINOGEN PLASMIN SYSTEM/

Citation
D. Albo et al., THROMBOSPONDIN-1 AND TRANSFORMING GROWTH FACTOR-BETA1 PROMOTE BREAST-TUMOR CELL INVASION THROUGH UP-REGULATION OF THE PLASMINOGEN PLASMIN SYSTEM/, Surgery, 122(2), 1997, pp. 493-499
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Surgery
Journal title
ISSN journal
0039-6060
Volume
122
Issue
2
Year of publication
1997
Pages
493 - 499
Database
ISI
SICI code
0039-6060(1997)122:2<493:TATGFP>2.0.ZU;2-G
Abstract
Background. Pericellular proteolysis is crucial in tumor cell invasion . The plasminogen/plasmin system is one of the main protease systems i nvolved in cancer progression. Thrombospondin-1 (TSP-1) through activa tion of transforming growth factor-beta 1 (TGF-beta 1) up-regulates th e main plasminogen activator the urokinase-type plasminogen activator (uPA). The objectives of this study were to determine the role of TSP- 1 and TGF-beta 1 in the localization of the plasminogen/plasmin system to the tumor cell surface by the uPA receptor (uPAR) and to determine its effect in breast tumor cell invasion. Methods. The effect of TSP- 1 and TGF-beta 1 in uPAR expression was determined in MDA-MB-231 human breast cancer cells by enzyme-linked immunosorbent assay and Western blot analysis. Their effect and the role of the plasminogen/plasmin sy stem in breast tumor cell invasion were studied with a Boyden Chamber assay. Results. uPAR expression was up-regulated more than twofold by both TSP-1 and TGF-P1. The effect of TSP-1 involved its receptor and t he activation of TGF-beta 1 by TSP-1. Breast tumor cell invasion was u p-regulated sevenfold to eightfold by both TSP-1 and TGF-beta 2 compar ed with the control group. Antibodies against uPA or uPAR neutralized the TSP-1- and TGF beta 1-promoted breast tumor cell invasion. Conclus ions. TSP-1, through the activation of endogenous TGF-beta 1, up-regul ates the plasminogen/plasmin system and promotes tumor cell invasion i n breast cancer cells.