Differential expression of lysophosphatidic acid (LPA) receptors in human ovarian carcinomas

Objective: Aims of this study was to explore the expression of three lysophosphatidic acid (LPA) receptors, LPA1, LPA2, and LPA3, at mRNA and protein levels, and their possible mechanisms and biological significance in human ovarian carcinomas (OC). Materials and Methods: Seventy-seven cases of epithelial OC were confirmed by histological classification: 53 cases were serous OC, 16 were endometrioid OC, three were mucinous OC, and the remaining five were ovarian clear cell carcinoma and others. Additionally, there were 42 patients with well-differentiated to moderately differentiated OC, 35 with poorly differentiated OC, 17 cases of recurrent OC, 60 cases of non-recurrent, 17 cases of borderline tumors, and 28 cases were benign OC. Normal ovarian epithelium (n = 8, 2-3 mmthick) from patients with uterine fibroids were chosen as the healthy controls. Reverse transcription-polymerase chain reaction (RT-PCR) detected LPA1-3 mRNA expression levels. Immunohistochemical (IHC) staining was used to identify the LPA receptors protein expression. Results: LPA1 mRNA and protein levels were significantly lower in epithelial OC than in normal ovarian epithelium, benign ovarian tumor, and borderline tumors, and the converse was true for LPA2 and LPA3. Furthermore, the mRNA and protein levels of LPA receptors showed no statistical significant differences among those OC patients in different histological tumor subtypes; similar results were also presented in those cases of different degrees of differentiation and LPA1 mRNA level was significantly lower in patients with recurrent OC compared to those with non-recurrent OC, yet no significant difference was observed regarding the protein expression of LPA1. In addition, the mRNA and protein expression levels of LPA2 and LPA3 were both apparently higher in patients with recurrent OC than those with non-recurrent OC. Conclusion: LPA and its receptors could have important roles in OC. Upregulated expression of LPA1 inhibits growth of OC, implying LPA1 could be a novel therapeutic target in OC. LPA2 and LPA3 are relevant to metastatic behavior and could be used as prognostic indicators in OC.

Epithelial ovarian carcinomas; Lysophosphatidic acid; Lysophosphatidic acid receptors; Reverse transcription-polymerase chain reaction; Immunohistochemical staining; Borderline tumors; Recurrent; Non-recurrent.

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