Stromal-cell derived factor-1 regulates epithelial ovarian cancer cell invasion by activating matrix metalloproteinase-9 and matrix metalloproteinase-2

The aim of this study was to test the hypothesis that stromal-cell derived factor-1 (SDF-1)/chemokine receptor type 4 (CXCR4)-mediated metastasis of ovarian cancer cells to peritoneal cavity would be related with matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) activation. Invasion assay was used to evaluate the functional interaction between SDF-1 and CXCR4. Real-time polymerase chain reaction was performed to analyze the changes of CXCR4, MMP-2 and MMP-9 at the mRNA level upon SDF-1 stimulation. Western blot was used for observing the changes of CXCR4 protein expression and zymograph assay for comparing MMP-2 and MMP-9 activities after SDF-1 induction. In ovarian cancer cells, SDF-1 stimulation resulted in increased CXCR4 expression at both the transcription and protein levels. SDF-1 increased cell invasion in a CXCR4-dependent manner, and this increase was related with the activation of MMPs. Moreover, SDF-1-CXCR4 interaction activated MMP-9 at the both transcription and protein levels and MMP-2 only at the post-translation level. SDF-1-CXCR4 interaction confers on ovarian cancer cells a remarkable potential to activate MMPs for subsequently invading the peritoneal cavity.