Effects Of Stromal Cell-derived Factor-1 And Its Receptor On The Biological Behavior Of Epithelial Ovarian Tumor

Part OneExpression of Stromal Cell-derived Factor-1 and its Receptor inEpithelial Ovarian TumorObjective To explore the expressions of stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 in epithelial ovarian tumor.Methods The expression of SDF-1/CXCR4 at mRNA and protein level were measured by RT-PCR, western blot and immunohistocheniical technique in 22 cases of ovarian cancers, 8 cases of ovarian borderline tumors, 10 cases of ovarian benign tumors and 10 cases of normal ovary tissues.Results Strongly positive expressions of SDF-1/CXCR4 protein are observed in cancer cells and stromal cells in ovarian cancer, while negative or weakly positive expression of SDF-1/CXCR4 protein are found in epithelial cells and stromal cells in ovarian borderline tumors, ovarian benign tumors and normal ovary tissues. The expression of SDF-1/CXCR4 in ovarian cancers at mRNA and protein level were significantly higher than that of ovarian borderline tumors, ovarian benign tumors and normal ovary tissues (P < 0.01, P < 0.01, respectively ). Of all ovarian cancers, the expressions of SDF-1/CXCR4 in cases with lymph metastasis were significantly higher than that of cases without lymph metastasis (P < 0.05). The expression of SDF-1/CXCR4 in ovarian cancers were not associated to differences of clinical stages, histological grades and pathological types (P > 0.05).Conclusion SDF-1 and its receptor CXCR4 are highly expressed in ovarian cancer, which may be related with lymph metastasis of ovarian cancer.Part TwoImpacts of Stromal Cell-derived Factor-1 and its Receptor on theBiological Behavior of Ovarian Cancer CellsObjective To explore the expressions of stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 in human ovarian cancer cell line CAOV3, 0VCAR3, SKOV3 and COC1 as well as to investigate the impacts of SDF-1/CXCR4 on human ovarian cancer cells, such as growth, proliferation, chemotaxis and invasion.Methods The expressions of SDF-1/CXCR4 at mRNA and protein lexels were measured by RT-PCR and western blot technique in ovarian cancer cells. After treatment with recombinant human SDF-1 or anti-human CXCR4 monoclonal antibody, the proliferation of ovarian cancer cells was detected with MTT method, the cell cycle and apoptosis were observed with flow cytometry, PCNA expression was detected with immunohistochemical technique and Transwell was used to evaluate the impacts on chemotaxis and invasion of ovarian cancer cells.Results In human ovarian cancer cell line CA0V3, OVCAR3, SKOV3 and COC1, the expression of CXCR4 were detected at mRNA and protein level. Onn contrast, the expression of SDF-1 were not detected at either mRNA or protein level. After treatment with recombinant human SDF-1, the proliferation of cells was increased, S phase arrest was observed in cells, the expression of PCNA was highly increased. Similarly, more invasive properties were displayed in the cancer cell treated with SDF-1compared to that in the control group( P < 0.05 ). Anti-human CXCR4 monoclonal antibody may block these effects at certain level.Conclusion The interaction of stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 may accelerate the abilities of proliferation, chemotaxis and invasion in ovarian cancer cells.Part ThreeImpacts on the Biological Behavior of Ovarian Cancer in vivo byBlocking Stromal Cell-derived Factor-1 and its ReceptorObjective To explore the impacts on the biological behavior of Ovarian Cancer in vivo by Blocking Stromal Cell-derived Factor-1 and its ReceptorMethods After blocking SDF-1 receptor CXCR4 with anti-human CXCR4 monoclonal antibody, ovarian cancer cell line CAOV3 were subcutaneously in nude mice. The time of formation tumor, tumor volumes, formation tumor rates, survival duration and lymph node metastasis rates were observed.Results There were significant differences between the test group and the control group, on all the aspects of the time of formation tumor, tumor volumes, formation tumor rates, survival duration and lymph metastasis rates (P<0.05). There was no significant difference between control group and blank group (P>0.05).Conclusion Blocking out SDF-1 biologic activity with anti-human CXCR4 monoclonal antibody, the growth of ovarian cancer and lymph metastasis could be inhibited in some degree in vivo.