TUMOR-NECROSIS-FACTOR AND CELL-DEATH IN TUMORS (REVIEW)

Tumour necrosis factor (TNF) was initially described by Carswell et al (Proc Natl Acad Sci USA 72: 3666-3670, 1975) and was so named because of its massive lethal effect on some tumours, causing haemorrhagic necrosis, resulting in regression (Old LJ: Nature 326: 330-331, 1987). Two forms of TNF are now recognised, TNF-alpha and TNF-beta (lymphotoxin) and the TNF molecules have cell surface receptors, type 1 (TNF-R1) and type 2 (TNF-R2). On closer observation it was noted that not only pathological cell death (necrosis) resulted from treatment with TNF, but levels of physiological, gene-directed cell death (apoptosis) were also elevated (Haranaka K el al: Int J Cancer 34: 263-267, 1984; Sarraf CE, Bowen ID: Chemical Carcinogenesis 2, Modulating Factors. Plenum Press, pp 553-562, 1991). This review looks at the TNFs, their receptors and their relationships to apoptosis and necrosis in tumours.