Heterogeneity in response to interleukin 6 (IL-6), expression of IL-6 and IL-6 receptor mRNA in a panel of established human multiple myeloma cell lines.
The controversial role of interleukin-6 (IL-6) as an auto- or paracrine growth factor for human multiple myeloma (MM) cells was studied using a panel of six well characterized feeder-cell dependent and independent MM cell lines as models. With respect to the effect of IL-6 on growth and survival, three types of lines were found: (1) U-1958, dependent on IL-6 both for growth and survival; (2) U-1996, dependent on IL-6 for growth but not survival; and (3) U-266-1984, Fravel, L363, and Karpas 707, independent of IL-6. Feeder-cell supernatants were as efficient as feeder-cell monolayers in stimulating growth and contained IL-6 as the only growth promoting activity. IL-6 was growth stimulatory and sustained the growth of U-1958 only when the medium contained fetal calf serum. The nature of the serum factor(s) is unknown, but it was excluded to be the IL-6 carrier protein a2-macroglobulin. IL-1, IL-2, IL-3, TNF-alpha, GM-CSF, IGF-1, and insulin were neither co-stimulatory with IL-6 nor stimulated growth on their own. Only U-266-1984 expressed IL-6 mRNA. IL-6 receptor mRNA was expressed in all lines except the L363 and Fravel. We conclude that the response to IL-6 is heterogeneous among the MM lines and that IL-6 acts as a paracrine growth factor for two of six lines. In a third line, U-266-1984, the IL-6 mRNA expression suggests the possibility of an autocrine growth stimulation.
Jernberg
H
H
Department of Pathology, University of Uppsala, Sweden.
Pettersson
M
M
Kishimoto
T
T
Nilsson
K
K
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001402:B-Lymphocytes / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism
D000906:Antibodies; D003470:Culture Media; D007328:Insulin; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000511:alpha-Macroglobulins; D007334:Insulin-Like Growth Factor I