Tumor cells suppress cytokine-induced nitric-oxide (no) production in cerebral endothelial cells

✍ Scribed by Jun-Ichi Murata; Sally Betz Corradin; Robert Charles Janzer; Lucienne Juillerat-Jeanneret

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 770 KB
• Volume: 59
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910590519

✦ Synopsis

Nitric oxide (NO) produced by endothelial cells (EC) has been shown to exert cytotoxic activity on tumor cells. In order to analyze events involved in brain metastasis, the modulation of N O production in rat-brain-derived EC was investigated. N O release was increased by tumor necrosis factor-a (TNF-a), interferon-y (IFN-y), interleukin-18, lipopolysaccharide or forskolin in EC219 cells, a rat-brain-microvessel-derived EC line. Dexamethasone decreased N O release by cytokine-activated EC219 cells. Tumor cells (DHD/KIZ/PROb, a rat coloncarcinoma cell line) were highly adherent to EC219 cells, and adhesion was not modified by TNF-a plus IFN-y, or by dexamethasone. Addition of tumor cells or tumor-cell-conditioned medium significantly inhibited N O release induced by any of the stimuli examined, but only if added during the initial phase of endotheliai-cell activation, Tumor-derived suppression of NO release was also observed in primary cultures of cerebral EC. N O synthase (NOS) activity in cytosol extracts of the cerebral EC line was Ca2+-independent and required both NADPH and tetrahydrobiopterin. NOS activity was increased by TNF-a and IFN-y, and significantly reduced by tumor-cell-conditioned medium. These results suggest that rat colon-carcinoma cells may have developed a protective mechanism involving the release of (a) soluble factor(s) which inhibit@) NO production by cerebral EC.