Cytostatic and cytolytic effects of human recombinant tumor necrosis factor on human renal cell carcinoma cell lines derived from a single surgical specimen.

The purpose of this study was to determine whether human tumor cell lines derived from a single tumor exhibit heterogeneous responses to the anti-tumor effects of human recombinant tumor necrosis factor (h-r-TNF). Several cell lines with different metastatic propensities have been established in culture from a single surgical specimen of a human renal cell carcinoma following different selection procedures in nude mice. The cell lines exhibited significant differences in in vitro susceptibilities to cytotoxic effects of TNF. Kinetic analysis of the interaction of TNF with susceptible renal carcinoma cells demonstrated that a short 30 min interaction of TNF with the cells is sufficient to produce significant lysis 72 hr later. One cycle of exposure of sensitive cells to h-r-TNF did not produce cells resistant to it, nor did the degree of sensitivity to h-r-TNF vary after one passage of the cells in nude mice. Tumor cell resistance to the effects of TNF did develop spontaneously after prolonged cultivation in culture. We conclude that tumor cells derived from a single human renal cell carcinoma exhibit a heterogeneous response to the cytotoxic effects of h-r-TNF.