Requirement of CD45 and src family kinases for proliferation of myeloma cells by interleukin-6(Nakamura Prize)

Cytokines exert multiple biological functions through binding to their specific receptors that triggers activation of intracellular signaling cascades. The cytokine-mediated signals may produce variable and even opposing effects on different cell types, depending on cellular context that is also dictated by the differentiation stage of the cell. Multiple myeloma is a monoclonal proliferative disorder of human plasma cells. Despite the clonal origin of myeloma cells, they appear to include mixed subpopulations in accordance with the expression of their surface antigens, such as CD45, CD49e and MPC-1. Although interleukin-6 (IL-6) is widely accepted as the most relevant growth factor for myeloma cells in vitro and in vivo, only a few subpopulations of tumor cells, such as CD45^+MPC-1^-CD49e^- immature cells, proliferate in response to IL-6. We recently show that IL-6 efficiently activates both signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase 1/2 (ERK1/2) in CD45^- myeloma cell lines, although they fail to proliferate in response to IL-6. In contrast, src family protein-tyrosine kinases, the most important substrates for CD45 protein-tyrosine phosphatase is found activated independent of STAT3 and ERK1/2 activation in only CD45^+ but not CD45^- myeloma cell lines. Therefore, the activation of both STAT3 and ERK1/2 is not sufficient for IL-6-induced proliferation of myeloma cells that requires the src family kinase activation associated with CD45 expression. We propose a mechanism for IL-6-induced cell proliferation that is strictly dependent upon the cellular context in myelomas.

骨髄腫

細胞増殖

インターロイキン6

CD45

src型チロシンキナーゼ

本文データは山口大学医学会の許諾に基づきCiNiiから複製したものである