The role of CXCR4 and its ligand SDF-1α in the process of adhesion and invasion of ovarian cancer.

Objective:To explore the role of chemokine receptor 4(CXCR4) and its ligand stromal derived factor-1α(SDF-1α) in the processes of adhesion and invasion of ovarian cancer cells through activating the mitogen-activated protein kinases(MAPK) signaling pathway and its possible mechanism.Methods:Intracellular calcium mobilization in SKOV3 cells was detected with a laser scanning confocal fluorescence microscopy before and after SDF-1α treatment.Western blotting was used to detect the phosphorylation of extracellular signal-regulated kinase(ERK1/2) in SKOV3 cells after exposure to SDF-1α.Adhesion capability and matrix metalloproteinase(MMP) activity of ovarian cancer cells after exposure to SDF-1α were mesured by adhesion assay and gelatin zymography,respectively.Results:SDF-1α induced rapid intracellular calcium mobilization in a metastatic ovarian cancer cell line SKOV3,as well as rapid phosphorylation of ERK-1/2.Adhesion capability of ovarian cancer cells to fibronectin(FN) and collagen Ⅳ(COL) was increased by SDF-1α treatment,while the addition of PD98059,an inhibitor of ERK-1/2 signaling,reduced the effects of SDF-1α.SDF-1α also increased the activities of MMP-2 and MMP-9 secreted by SKOV3 cells.Conclusion:SDF-1α/CXCR4 regulates adhesion ability of ovarian cancer cells by activating MAPK signaling pathway and stimulates secretion of MMP-2 and MMP-9,thereby participates the processes of invasion and metastasis of ovarian cancer.