| Autor: |
Valérie Saint-Giorgio, Blandine Lieubeau, Patricia Lagadec, Jean-François Jeannin, Nathalie Onier, Stéphane Raynal, David A. Lawrence, Laurent Arnould |
| Rok vydání: |
1999 |
| Předmět: |
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| Zdroj: |
The American Journal of Pathology. 154:1867-1876 |
| ISSN: |
0002-9440 |
| DOI: |
10.1016/s0002-9440(10)65444-2 |
| Popis: |
Transforming growth factor-β1 (TGF-β1) has been shown to down-regulate NO synthesis in a variety of normal cells. In the present study, we investigated the influence of TGF-β1 upon NO production in tumor cells and its consequences for tumor development. During the growth of PROb colon carcinoma cells intraperitoneally injected in syngeneic BDIX rats, intratumoral concentration of TGF-β1 increases while NO concentration stays very low. Tumor regression induced by intraperitoneal injections of a lipid A is associated with a decrease in TGF-β1 and an increase in NO intratumoral concentration. In these tumors, PROb tumor cells are the NO- and TGF-β1-secreting cells. Using PROb cells transfected with an expression vector coding for TGF-β1 antisense mRNA, we demonstrate in vitro that there is an inverse correlation between the amount of TGF-β1 secreted and the ability of PROb cells to secrete NO. As the same results were obtained in the presence of an anti-TGF-β type II receptor neutralizing antibody, and as exogenous TGF-β1 is without any effect on NO secretion by PROb cells, TGF-β1 apparently down-regulates NO synthesis in PROb cells by an intracellular mechanism. These results suggest that endogenous TGF-β1 constitutes a potential target in a search for new antitumoral agents. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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