Autocrine IGF-1/IGF-1R signaling promotes cell migration and invasion in NK/T-cell lymphoma cells

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. Key words: NK/T-cell lymphoma; Insulin-like growth factor 1; Insulin-like growth factor 1 receptor; Autocrine; Cell migration; Cell invasion