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 murine 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 heterogeneity, which probably reflects overlapping effects of feeder cells, interleukin 6 (IL-6) and components of fetal calf serum (FCS) as well as tumour heterogeneity in vivo, has hampered the elucidation of molecular mechanisms underlying the effects of IL-6. In an attempt to dissociate growth and survival promotion of IL-6, we have studied two pairs of human MM cell lines, HL407E/HL407L and U-266-1970/U-266-1984, selected to represent different stages of in vitro tumour progression and 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 in HL407E cells; (c) no growth or survival promotion to U-266-1984. Moreover, 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 growth 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 separate events.
Spets
H
H
Department of Pathology, University Hospital, Uppsala, Sweden.
Jernberg-Wiklund
H
H
Sambade
C
C
Söderberg
O
O
Nilsson
K
K
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2