TUMOR-NECROSIS-FACTOR AND INTERFERON ARE SELECTIVELY CYTOSTATIC IN-VITRO FOR HORMONE-DEPENDENT AND HORMONE-INDEPENDENT HUMAN BREAST-CANCER CELLS

Since experimental studies have shown that tumour necrosis factor-alph a (TNF-alpha) has potent antitumour activity that can be potentiated w ith cytokines, we tested the efficacy of TNF-alpha with interferon-gam ma (IFN-gamma) on different human breast cancer cell lines, particular ly comparing hormone-dependent and -independent phenotypes. TNF-alpha inhibited the growth of hormone-dependent human MCF-7, ZR-75-1 and T47 -D breast cancer cells with a half maximal concentration of 0.25 nM. I n contrast, the growth of hormone-independent cells MDA-MB-231 and HS5 78T was not affected by TNF-alpha alone, but a synergistic inhibition was observed when using IFN-gamma and TNF-alpha together. The mRNA for the proto-oncogene C-MYC, as an intracellular indicator of cell activ ation, was significantly increased in MCF-7 cells in the presence of T NF-alpha. In MDA-MB-231 cells this mRNA was increased only in the pres ence of both TNF-alpha and IFN-gamma, without a change in the number o f surface TNF receptors. These findings indicate that TNF-alpha treatm ent in combination with IFN-gamma may provide a successful approach to overcome the cellular heterogeneity of advanced breast tumours. Copyr ight (C) 1996 Elsevier Science Ltd