Abstract 3011: Differential expressions of lysophospholipid receptors (LPRs) in benign and malignant tissues from various human system/organs

Abstract

Abstract Background: Lysophospholipid receptors (LPRs), including Lysophosphatidic acid (LPA) receptors and sphingosine 1-phosphate (S1P) receptors, are a group of G protein-coupled receptors. LPRs are involved in a wide range of biological processes, such as embryogenesis, systemic development, immune cell trafficking, and inflammatory reactions. The emerging evidence has suggested that the activities of LPRs may be associated with pathogenesis and metastasis of several human cancers. In this study, the expression levels of several LPRs were determined by immunohistochemistry (IHC) in various benign and malignant tissues from various human system/organs, in order to correlate the expression levels of these LPRs with different malignancies. Methods: IHC for EDG1 (S1P receptor 1, S1P1, C- and N-terminals), EDG8 (S1P receptor 5, S1P5), EDG2 (LPA receptor 1, LPA1) and EDG4 (LPA receptor 2, LPA2) was performed on tissue microarray slides containing 384 formalin-fixed paraffin-embedded benign and malignant tissues from 33 human system/organs. The expression level of each LPR was reported as a final IHC score calculated as staining extent score (0-3) multiplied by intensity score (0-3) with a maximal score of 9. Student t-test was employed to analyze the differences in IHC score of each studied LPR between benign and malignant tissues in overall and in individual system/organ. Results: The IHC signals for all studied LPRs were seen in both cytoplasm and nuclei of most tissues. In the level of overall benign and malignant tissues, the expression pattern was similar for all studied LPRs: the cytoplasmic IHC signals were decreased, but the nuclear IHC signals were increased in malignant tissues as compared with benign tissues. Among them, the expression level of cytoplasmic S1P1 (C-terminal) was significantly decreased, and expression levels of nuclear S1P1 (N-terminal) and LPA1 were significantly increased in overall malignant tissues as compared with overall benign tissues. At the organ level, a significant increase in nuclear expression was observed in liver malignancies for all studied LPRs, whereas a decrease in nuclear expression was observed in lung malignancies for all studied LPRs. In colon malignancies, the expression levels of S1P1 (both N- and C-terminals) were significantly increased, but the expression level of LPA1 was significantly increased as compared with benign colon tissues. Conclusion: The constitutive expression of cytoplasmic LPRs may be essential for physiological processes in all tissues. However alterations in nuclear expression of studied LPRs may differentially correlate with the tumorogenesis in different system/organs. Citation Format: Chunyi Wang, Samantha Redfield, Jinghe Mao, Yinyuan Mo, Xinchun Zhou. Differential expressions of lysophospholipid receptors (LPRs) in benign and malignant tissues from various human system/organs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3011. doi:10.1158/1538-7445.AM2014-3011