Autocrine IGF-1/IGF-1R signaling promotes cell migration and invasion in NK/T-cell lymphoma cells / 白血病·淋巴瘤

ABSTRACT

Objective To identify the expression pattern of IGF-1 and IGF-1R in NK/T-cell lymphoma (NK/TCL) cell lines and to investigate the role of IGF-1/IGF-1R signaling in regulation of cell migration and invasion.Methods RT-PCR and immunofluorescence were performed to detect the expression of IGF-1 and IGF-1R.Transwell assay was applied to observe the effects of IGF-1/IGF-1R signaling and downstream kinases activities on cell migration and invasion.Concentrations of MMP-2 and MMP-9 were quantified by ELISA.Results Co-expression of IGF-1 and its receptor IGF-1R were identified in two NK/TCL cell lines,SNK-1 and SNK-6,while normal NK cells lack the IGF-1R expression.IGF-1R inhibitors significantly reduced SNK-1 and SNK-6 cells migration and invasion rates.Exogenous IGF-1 promoted both cell lines migration and invasion,but these effects were both blocked by IGF-1R inhibitors.Inhibition of AKT,p38 and JNK,the possible IGF-1R downstream kinases,reduced cell migration rates.Further more,exogenous IGF-1 significantly increased MMP-2 and MMP-9 secretion,while decreased secretion of MMP-2 and MMP-9 were observed when IGF-1R inhibitors were applied.Conclusion An autocrine IGF-1/IGF-1R signaling loop is aberrantly expressed on NK/TCL cells and the autocrine loop significantly promotes cell migration and invasion through activation of p38,PI3K and JNK signaling and enhances secretion of MMP-2 and MMP-9.