Upregulation of PRL-3 increased myeloma cell viability and rephosphorylated STAT3 in a biphasic manner through direct interaction and deactivation of SHP2, thus blocking the gp130 (Y759)-mediated repression of STAT3 activity.
Recent investigations of the cytokine network surrounding myeloma cells have disclosed the importance of gp130-related cytokines including interleukin (IL)-6 for myeloma cell survival and proliferation, identification of IL-10 as a growth factor for myeloma cells, the close relationship between IL-10 and the receptors for gp130-related cytokines, and the growth enhancement effect of IL-11 and IL-7 on myeloma cells.
Finally, combining CD126 and CD130 expression we found a significant increase of the percentage of CD126+ CD130+ patients at relapse, underlying the crucial role of IL-6 response in the late stage of MM.
Moreover, because gp130-mediated signaling results in myeloma cell growth, autocrine expression of any gp130-utilizing cytokine has the potential to significantly augment tumor expansion.