Increase in interleukin 6 (IL-6) and IL-6 receptor expression in a human multiple myeloma cell line, U-266, during long-term in vitro culture and the development of a possible autocrine IL-6 loop.
A human multiple myeloma (MM) cell line, U-266, has developed the ability to grow independently of exogenous interleukin 6 (IL-6) during long-term cultivation in vitro. The early passage, feeder-cell dependent U-266 cell line (U-266-1970) was compared with the late passage U-266-1984 cell line with respect to response to IL-6, IL-1 beta and tumour necrosis factor alpha and expression of IL-6 and IL-6 receptor (IL-6R) mRNA and protein. The results showed that; (a) only the U-266-1970 cell line was stimulated to growth by IL-6, (b) IL-6 and IL-6R mRNA were expressed in both cell lines, (c) the level of IL-6 mRNA was increased in the U-266-1984 cell line and only this line produced IL-6 and, (d) the level of IL-6R mRNA was highest in the U-266-1984 cell line and the number of IL-6R about ten times higher than in U-266-1970. The growth of the IL-6-producing U-266-1984 cell line was inhibited by 30% by anti-IL-6R antibodies suggesting the possibility that an autocrine IL-6 loop might have developed during the long-term cultivation. In addition to many other phenotypic alterations of the U-266 cell line, having developed as a consequence of tumor progression in vitro, its growth factor requirement seems to have evolved from a dependence on IL-6 as a paracrine growth factor to a capacity for autonomous growth, dependent on autocrine IL-6 stimulation. Whether such a development also may take place in MM clones in vivo remains to be established.
Jernberg-Wiklund
H
H
Department of Pathology, University of Uppsala, Sweden.
Pettersson
M
M
Carlsson
M
M
Nilsson
K
K
D015152:Blotting, Northern; D015139:Blotting, Southern; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000276:immunology
D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6