[The mechanism of polypeptide derived from viral macrophage inflammatory protein II modulates SDF-1α/CXCR4-induced migration].
OBJECTIVE
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 Ca(2+); 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(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).


CONCLUSIONS
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.
Department of Biochemistry & Molecular Biology, Bengbu Medical College, Bengbu, China. yqlmimi@163.com
Qing-ling
QL
Yang
Yong-xing
YX
Ding
Chang-jie
CJ
Chen
Zhi-feng
ZF
Yang
Yan-jun
YJ
Gao
D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000276:immunology / Q000378:metabolism*; D018925:Chemokines / Q000737:chemistry* / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D054377:Chemokine CXCL12; D018925:Chemokines; D010455:Peptides; D019718:Receptors, CXCR4; C108059:vMIP-II; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium