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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Breast Neoplasms, Cell Adhesion Molecules, Female, Fibrinolysin, Gene Expression Regulation, Neoplastic, Humans, Membrane Glycoproteins, Neoplasm Invasiveness, Plasminogen, Receptors, Cell Surface, Receptors, Urokinase Plasminogen Activator, Thrombospondins, Transforming Growth Factor beta, Tumor Cells, Cultured, Up-Regulation.
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Do thrombospondin-1 and transforming growth factor-beta l promote breast tumor cell invasion through up-regulation of the plasminogen/plasmin system? Context: Pericellular proteolysis is crucial in tumor cell invasion. The plasminogen/plasmin system is one of the main protease systems involved in cancer progression. Thrombospondin-1 (TSP-1), through activation of transforming growth factor-beta 1 (TGF-beta 1), up-regulates the 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. 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 system in breast tumor cell invasion were studied with a Boyden Chamber assay. uPAR expression was up-regulated more than twofold by both TSP-1 and TGF-beta 1. The effect of TSP-1 involved its receptor and the activation of TGF-beta 1 by TSP-1. Breast tumor cell invasion was up-regulated sevenfold to eightfold by both TSP-1 and TGF-beta 1 compared with the control group. Antibodies against uPA or uPAR neutralized the TSP-1- and TGF-beta 1-promoted breast tumor cell invasion.
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TSP-1, through the activation of endogenous TGF-beta 1, up-regulates the plasminogen/plasmin system and promotes tumor cell invasion in breast cancer cells. Final Decision: yes