MECHANISM OF MACROPHAGE RECOGNITION OF TUMOR CELLS

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Macrophages are believed to be an important component of tumor surveillance in vivo. They are thought to be an excellent mechanism of tumor destruction, as they will kill tumor cells while leaving normal cells undisturbed. The process of macrophage lysis of tumor cells is now thought to be at least two identifiable steps--a recognition and binding step followed by the release of cytotoxic mediators by the macrophage. Although the steps in macrophage cytotoxicity have been well identified, the molecules or recognition structures that macrophages use to bind to tumor cells or to discriminate normal cells from neoplastic cells are unknown. Studies have isolated SV40-transformed tumor cells that were susceptible or resistant to in vitro cytolysis by LPS-activated murine macrophages. The presence of specific RNA tumor virus-induced gp70 was correlated with the resistance to lysis by macrophages. Using Friend leukemia virus (FLV)-transformed cells a different gp70, associated with cells susceptible to macrophage cytotoxicity and not with macrophage resistant FLV-transformed cells, was found. The studies suggest that gp70 may be involved in tumor recognition, but how it is involved is uncertain. Furthermore, involvement of other molecules has not been absolutely disproven. During this research, plans are to investigate the mechanism(s) of macrophage recognition of tumor cells and to biochemically define differences between cells killed or not killed by activated macrophages. (MB)