[The role and mechanism of CXCR4 and its ligand SDF-1 in the development of cervical cancer metastasis].

Background & Objective: The chemokine receptor CXCR4 and its sole ligand stromal cell-derived factor-1 (SDF-1) not only actively participate in inflammation, hematopoiesis, infection of HIV, but also play a pivotal role in migration, invasion and metastasis of some malignant tumors. This study was to investigate the role of CXCR4/SDF-1 axis in mediating metastasis in cervical cancer cells through activating the mitogen-activated protein kinase (MAPK) pathway and its possible mechanism.

Methods: Intracellular calcium mobilization was observed under laser scanning confocal fluorescence microscopy. The phospharylation of extracellular signal-regulated kinase (ERK) 1/2 in HeLa cells after binding of SDF-1alpha to CXCR4 was measured by Western blot. Adhesion of CXCR4/SDF-1 to cervical cancer cells and secretion of matrix metalloproteinase (MMP) were detected by adhesion assay and gelatin zymography, respectively.

Results: After SDF-1alpha was bound to CXCR4, a rapid and robust mobilization of intracellular calcium in Hela cells was initiated. The difference between the average baseline fluorescence intensity (FI) and the peak FI was significant (P < 0.01). ERK-1/2 was rapidly phosphorylated in Hela cells after its exposure to SDF-1alpha, and the strongest phosphorylation occurred at 30 min. The adhesion ability of Hela cells to fibronectin (FN) and laminin (LN) was increased after SDF-1alpha treatment (P < 0.05 and P < 0.01, respectively), while pretreatment of Hela cells with an ERK-1/2 inhibitor, PD98059, decreased adhesion of Hela cells to extracellular matrix (ECM) with the presence of SDF-1alpha (P < 0.05). Increased amounts of active MMP-2 were secreted in response to increased SDF-1alpha concentrations. When the concentration of SDF-1alpha was 800ng/mL, the secretion of active MMP-2 reached the peak and started to decrease afterwards.

Conclusion: CXCR4/SDF-1 participates in tumor invasiveness and metastasis in cervical cancer through regulating the adhesion ability by activating the MAPK signaling transduction pathway and promoting secretion of MMP-2.