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

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.

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 Ca(2+); concentration was measured by fluorometric analysis. Western blot analyses were performed to quantify phosphorylated ERK1/2 and FAK expression levels.

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(P<0.05). NT21MP also blocked Ca(2+); influx(P<0.05), an important signal for SKBR3 migration. In addition, NT21MP significantly decreased SDF-1α-induced SKBR3 migration and downregulated SDF-1α-induced express of phospho-ERK1/2 and phospho-FAK(P<0.05).

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 Ca(2+); influx and the downstream reduction of ERK1/2 and FAK signals.