Impaired angiogenic balance and suppression of tumorigenicity in HeLa cells chronically exposed to interferon-alpha

We have previously reported that IFN alpha -chronic treatment for 41 days i nduced a partial phenotype reversion on HeLa cells along with a down-regula tion of HPV18 mRNA levels. However, tumorigenicity of these cells in nude m ice was unchanged. Interestingly, after 1 year of IFN alpha -chronic exposi tion, HeLa cells failed to induce s.c. tumors when injected into nude mice. In such experimental conditions both HPV18 DNA integration pattern and vir al DNA copy number present in HeLa cells remained intact in the nontumorige nic phenotype cells. As result of the treatment with IFN alpha, HeLa cells rendered more resistant to lysis mediated by activated natural killer cells in vitro. Furthermore, IFN alpha -chronic treatment was able to induce VEG F and decrease bFGF mRNA expression, suggesting a potential effect on the a ngiogenic behavior of these tumoral cells, Thus, long-term treatment of HeL a cells with IFN alpha can accomplish a reversion of the malignant phenotyp e by a sequential multistep mechanism, in which the antiangiogenic effect o f IFN alpha could be one of the contributing events. (C) 2000 Academic Pres s.