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 LPA(1), LPA(2) and LPA(3) mRNA, LPA(2) and LPA(3) 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 LPA(2) and LPA(3) protein expression in cultured human ovarian cancer cell lines.
Results: RT-PCR revealed that all ovarian cancer cell lines expressed LPA(1), LPA(2) and LPA(3) mRNA. The positive rates (100%; 86.4%; 88.2%) of LPA(1) mRNA in normal ovarian tissue, benign tumor and ovarian cancer were no significant difference (p>0.05). The expression level of LPA(1) mRNA was significantly higher in normal ovarian tissue compared with that in benign tumor and in ovarian cancer tissue (p<0.01). LPA(1) expression level was no significant difference in both benign tumor and ovarian cancer tissue (p>0.05). LPA(2) 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); LPA(2) mRNA-positive rates and expression level were no significant difference in both benign tumor and normal ovarian tissue (p>0.05). LPA(3) 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), LPA(3) mRNA-positive rates and expression level were no significant difference in both benign tumor and normal ovarian tissue (p>0.05). LPA(1) mRNA expression level was significantly decreased compared with that of LPA(2) and LPA(3) in ovarian cancer (p<0.01); Western blotting clearly revealed that all ovarian cancer cell lines showed LPA(2) and LPA(3) protein. The positive rates and expression level of LPA(2) and LPA(3) 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); LPA(2) and LPA(3) 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 LPA(2) and LPA(3) 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 G(3) was significantly higher compared with grade G(1) (p<0.05).
Conclusion: LPA(1), LPA(2) and LPA(3) mRNA and protein expressed widely in human epithelial ovarian neoplasms. LPA(2) and LPA(3) may be involved in the development and progression of human ovarian cancer. There was a significant correlation between LPA(2), LPA(3) and invasion and metastasis of epithelial ovarian cancer. LPA(2) and LPA(3) may be a prognostic indicator in patients with epithelial ovarian cancer.