LOW/HIGH PROLIFERATION RATE of HUMAN MYELOMA CELLS. INVESTIGATION of INTERLEUKIN-6 and INTERLEUKIN-6 RECEPTOR ANTAGONIST

Abstract

Multiple myeloma (MM) is characterised as a malignant plasma cells proliferation. Interleukin-6 (IL-6) is a major proliferative factor for the malignant plasma cells. Interleukin-6 mediates its function by building a complex with the membrane-bound IL-6 receptor (IL-6R).
Aim: To investigate the effect of exogenous IL-6 and IL-6 receptor antagonist (IL-6RA) on the proliferation and on the membrane expression of IL-6 receptor in human myeloma cell lines (a) having low spontaneous proliferation rate, (b) having high spontaneous proliferation rate.
Materials and Methods: Three human multiple myeloma cell lines (RPMI-8226, OPM2 and LP-1) were investigated in an in vitro model. Measured parameters: Viability, Membrane expression of IL-6 receptor, Cell proliferation.
Results: IL-6 enhanced the proliferation in all myeloma cell lines with low spontaneous proliferation rate. In cell lines having high spontaneous proliferation IL-6 was ineffective. IL-6RA did not affect the spontaneous proliferation in the both groups.
IL-6 up-regulated its membrane-bound receptor markedly in cells having low proliferation or high proliferation rate. IL-6RA reduced the membrane expression of IL-6 receptor down to an average of 55% (cells with low spontaneous proliferation ) resp. 77% (cells with high spontaneous proliferation) in the investigated cell lines.
Conclusion: The findings indicate that cells with low spontaneous proliferation have autocrine and paracrine regulation mechanisms, the cells with high spontaneous proliferation only an autocrine regulation mechanism. By the stromal cells produced IL-6 enhances the proliferation of myeloma cells with low spontaneous proliferation. This fact justifies the use of substances with cytostatic effect to inhibit the proliferation of myeloma cells.