The lysophosphatidic acid (LPA) receptors their expression and significance in epithelial ovarian neoplasms

Objective.To investigate the lysophosphatidic acid (LPA) receptors expression situation and their biological significance in human ovarian cancer cell lines and in human epithelial ovarian neoplasms.Methods.The reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were employed to measure the expression levels of LPA1, LPA2 and LPA3 mRNA, LPA2 and LPA3 protein expression in cultured human ovarian cancer cell lines (3AO, SKOV3 and OVCAR3) and in human epithelial ovarian neoplasms. The immunocytochemical method was used to detect LPA2 and LPA3 protein expression in cultured human ovarian cancer cell lines.Results.RT-PCR revealed that all ovarian cancer cell lines expressed LPA1, LPA2 and LPA3 mRNA. The positive rates (100%; 86.4%; 88.2%) of LPA1 mRNA in normal ovarian tissue, benign tumor and ovarian cancer were no significant difference (p > 0.05). The expression level of LPA1 mRNA was significantly higher in normal ovarian tissue compared with that in benign tumor and in ovarian cancer tissue (p < 0.01). LPA1 expression level was no significant difference in both benign tumor and ovarian cancer tissue (p > 0.05). LPA2 mRNA-positive rates (92.6%) and expression level were significantly higher in ovarian cancer compared with that in benign tumor (31.8%) and in normal ovarian tissue (31.3%) (p < 0.01); LPA2 mRNA-positive rates and expression level were no significant difference in both benign tumor and normal ovarian tissue (p > 0.05). LPA3 mRNA-positive rates (92.6%) and expression level were significantly higher in ovarian cancer compared with that in benign tumor (31.8%) and in normal ovarian tissue (31.3%) (p < 0.01), LPA3 mRNA-positive rates and expression level were no significant difference in both benign tumor and normal ovarian tissue (p > 0.05). LPA1 mRNA expression level was significantly decreased compared with that of LPA2 and LPA3 in ovarian cancer (p < 0.01); Western blotting clearly revealed that all ovarian cancer cell lines showed LPA2 and LPA3 protein. The positive rates and expression level of LPA2 and LPA3 protein were significantly increased in ovarian cancer (92.6%; 92.6%) compared with that in benign tumor (45.5%; 45.5%) and that in normal ovarian tissue (43.8%; 43.8%) (p < 0.01); LPA2 and LPA3 protein-positive rates and expression level were no significant difference in both benign tumor and normal ovarian tissue (p > 0.05). Correlation of clinicopathological parameters showed that LPA receptors mRNA and protein expression were associated with FIGO stage and histological grade, except pathologic types and age. The mRNA and protein expression of LPA2 and LPA3 in stages III and IV was significantly higher than that in stages I and II epithelial ovarian cancer (p < 0.05). The mRNA and protein expression of pathologic grade G3 was significantly higher compared with grade G1 (p < 0.05).Conclusion.LPA1, LPA2 and LPA3 mRNA and protein expressed widely in human epithelial ovarian neoplasms. LPA2 and LPA3 may be involved in the development and progression of human ovarian cancer. There was a significant correlation between LPA2, LPA3 and invasion and metastasis of epithelial ovarian cancer. LPA2 and LPA3 may be a prognostic indicator in patients with epithelial ovarian cancer.