How does interleukin-6 affect the membrane expressions of interleukin-6 receptor and gp130 and the proliferation of the human myeloma cell line OPM-2?
Interleukin-6 (IL-6) is a potent growth factor for the proliferation of multiple myeloma (MM), which accounts for 1-2% of all human cancers. In this study we investigated the effects of IL-6 in various doses on the following parameters in the human myeloma cell line OPM-2: membrane expression of IL-6 receptor (IL-6R) and gp130, proliferation of the tumour cells and the amount of the soluble IL-6 receptor (sIL-6R) in the supernatant. Additionally, we tested the same parameters with the immunomodulator Viscum album (VA) extract. The expression of surface IL-6R and gp130 was analysed by FACS, the measurements of proliferation using the BrdU incorporation during DNA synthesis, and the determination of sIL-6R in the supernatant by ELISA. OPM-2 cells proliferate spontaneously (doubling time: 48 h), IL-6-production was not detectable. The exogenous IL-6 upregulated its own receptor up to a mean of 180% of controls at 5 ng/ml (P < 0.001), higher or lower doses were less effective. The membrane expression of gp130 was downregulated to 1-2%. IL-6 led to increase of the sIL-6R in the supernatant (P < 0.001) and raised the proliferation of the myeloma cells up to a mean of 124% (P < 0.001). These results indicate that the human myeloma cell line OPM-2 has an autocrine IL-6 regulation mechanism, with an additional paracrine signalling by exogenous IL-6. This is the first report that IL-6 inhibits the membrane expression of gp130, although the proliferation of the myeloma cells increases. VA extract did not affect survival, the expression of surface receptors IL-6 and gp130 or the amount of sIL-6R in the supernatant. However, the proliferation of the tumour cells was inhibited significantly (P < 0.05) suggesting a possible arrest in the cell cycle.
Kovacs
Eva
E
Society of Cancer Research, Kirschweg 9, 4144 Arlesheim, Switzerland. evakovacsbenke@hotmail.com
D015703:Antigens, CD / Q000096:biosynthesis* / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D050822:Cytokine Receptor gp130; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000187:drug effects; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology*; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis* / Q000187:drug effects
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130