THE EFFECTS ON GROWTH AND SURVIVAL OF IL-6 CAN BE DISSOCIATED IN THE U-266-1970 U-266-1984 AND HL407E/HL407L HUMAN MULTIPLE-MYELOMA CELL-LINES/

Several studies have documented IL-6-dependent growth promotion of mur ine and human neoplastic plasma cells. However, it is well known that human multiple myeloma (MM) cells in vitro show a considerable degree of heterogeneity concerning growth and survival requirements. This het erogeneity, which probably reflects over-lapping effects of feeder cel ls, interleukin 6 (IL-6) and components of fetal calf serum (FCS) as w ell as tumour heterogeneity in vivo, has hampered the elucidation of m olecular mechanism underlying the effects of IL-6. In an attempt to di ssociate growth and survival promotion of IL-6, we have studied two pa irs of human MM cell lines, HL407E/HL407L and U-266-1970/U-266-1984, s elected to represent different stages of in vitro tumour progression a nd dependence of feeder cells and exogenous IL-6. We demonstrated that exogenous IL-6, in the presence of FCS, conveyed: (a) a strong growth stimulatory effect with weak or no survival promotion in HL407L and U -266-1970 cells; (b) promotion of survival with no effects on growth i n HL407E cells; (c) no growth or survival promotion to U-266-1984. Mor eover, our results suggested that IL-6 may enhance apoptosis in U-266- 1970/U-266-1984 cells, and that FCS may interfere with IL-6 in its gro wth stimulatory effect. The relative dissociation of growth, survival and apoptotic effects of IL-6 leads to the conclusion that the HL407E/ HL407L and U-266-1970/U-266-1984 pairs of cell lines provide a useful human model system to study molecular mechanisms underlying these sepa rate events.