Anti-tumor activity of cytokines against opportunistic vascular tumors in mice

✍ Scribed by Qiang G. Dong; Andrea Graziani; Cecilia Garlanda; Rosa Wainstock de Calmanovici; Marco Arese; Rafaella Soldi; Annunciata Vecchi; Alberto Mantovani; Federico Bussolino

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 966 KB
• Volume: 65
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19960301)65:5<700::aid-ijc23>3.0.co;2-9

✦ Synopsis

Polyoma middle T (PmT)-transformed endothelial cells may represent a unique murine model for human opportunistic vascular tumors. The present study was designed to evaluate the anti-tumor potential of a panel of 13 cytokines against rnurine PmT-transformed endothelial cells. Interferon gamma (IFNy) and transforming growth factor beta I (TGFp I) substantially decreased in a dose-dependent manner the proliferation of a panel of 6 PmT-transformed cell lines. IFNa and tumor necrosis factor a (TNFa) had marginal anti-proliferative activity, whereas other molecules (interleukins-I, -2, -4, -6 and -13, IFNB, leukemia inhibitory factor, oncostatin M, granulocytemacrophage colony-stimulating factor) caused no growth inhibition. IFNy and TGFpl were therefore selected for further analysis of their mechanism of action and in vivo relevance. IFNy and TGFp I reduced the activity of phosphatidylinositol-3- kinase and the production of phosphatidylinositol 3,4-biphosphate, without modifying the tyrosine kinase(s) activity associated with PmT. IFNy and TGFPl were also tested for their ability to modify the in vivo growth of the PmT-transformed endothelial cells HSV in syngeneic C57B1/6 mice. Treatment with IFNy and TGFp I significantly delayed tumor growth and increased survival time. In contrast, treatment with IFNa and TNFa failed to prolong survival. In nude mice, IFNy and TGFp I had a transient effect on tumor growth but no effect on survival, suggesting a contribution of T cells to the in vivo anti-tumor activity of these cytokines.