[The mechanism of polypeptide derived from viral macrophage inflammatory protein II modulates SDF-1α/CXCR4-induced migration].

AIM: To assess whether NT21MP,the synthetic antagonist 21-mer peptide derived from viral macrophage inflammatory protein Ⅱ inhibits human SKBR3 cells migration by interfering with SDF-1α/CXCR4 signaling.METHODS: The levels of CXCR4 were detected in breast cancer cells SKBR3 and MCF-7 by RT-PCR and immunohistochemistry.The effect of SDF-1α-induced SKBR3 migration(chemotaxis) in the presence and absence of NT21MP was determined using the Boyden chamber migration assay.Intracellular Ca2+ concentration was measured by fluorometric analysis.Western blot analyses were performed to quantify phosphorylated ERK1/2 and FAK expression levels.RESULTS: The expression of CXCR4 was higher in SKBR3 than MCF-7 cells;SKBR3 migration increased in SDF-1α-treated cells.In contrast,AMD3100,an inhibitor of CXCR4 effectively inhibited SKBR3 migration.SKBR3 migration was decreased when the cells were exposed to NT21MPdose dependently(P0.05).NT21MP also blocked Ca2+ influx(P0.05),an important signal for SKBR3 migration.In addition,NT21MP signiflcantly decreased SDF-1α-induced SKBR3 migration and downregulated SDF-1α-induced expres of phospho-ERK1/2 and phospho-FAK(P0.05).CONCLUSION: The results showed that NT21MP has an inhibitory effect on SDF-1α-induced SKBR3 migration.The plausible mechanism of action could be upstream blockage of Ca2+ influx and the downstream reduction of ERK1/2 and FAK signals.