The role of SDF-1/CXCR4 axis in ovarian cancer metastasis.
This study was aimed to explore the role of stromal-derived factor 1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis in mediating the metastasis of ovarian cancer cells through activation of extracellular signal-regulated kinase-1/2 (ERK-1/2) signaling pathway. A highly metastatic ovarian cancer cell line, SKOV3, was used in the study. Intracellular calcium mobilization was detected by using laser scanning confocal fluorescence microscopy. Western blotting was used to detect the phosphorylation of ERK1/2 in SDF-1alpha-treated SKOV3 cells. Adhesion capability and matrix metalloproteinase (MMP) activity of ovarian cancer cells after exposure to SDF-1alpha were measured by adhesion assay and gelatin zymography. The results showed that SDF-1alpha induced rapid intracellular calcium mobilization in SKOV3 cells, as well as the phosphorylation of ERK-1/2. The adhesion of ovarian cancer cells to fibronectin and collagen IV was increased after SDF-1alpha treatment. An inhibitor of ERK-1/2 signaling, PD98059, could antagonize such effects of SDF-1alpha. SDF-1alpha could also increase the secretion of active MMP-2 and MMP-9. It was concluded that the SDF-1/CXCR4 axis played a critical role in the metastasis of human ovarian cancer by increasing the adhesion capability of cancer cells and the activity of MMP-2 and MMP-9 via ERK1/2 signaling pathway.
Shen
Xiaoyan
X
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. shen_xiaoyan45@yahoo.com.cn
Wang
Shaohai
S
Wang
Hongbo
H
Liang
Minglin
M
Xiao
Lan
L
Wang
Zehua
Z
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9