Abstract 5003: Differential expression of lysophosphatidic acid receptors (LPARs) between benign and malignant tissues in humans

Abstract

Abstract Background: Lysophosphatidic acid receptors (LPARs) are important to normal cellular functions and implicated in the pathogenesis and survival of various cancers recently. Previous studies were mostly focused on one LPAR using experiments on animal models and cell cultures. This study was executed to investigate systemic distribution of LPAR1, LPAR2, and LPAR3 in human organs/tissues and to compare the expression levels of these receptors between benign and malignant changes in major human organs/tissues. Method: Tissue Microarrays TMAs) were constructed with 384 formalin-fixed and paraffin-embedded benign and malignant specimens from 33 different human organs/tissues. Immunohistochemistry (IHC) for each LPAR was performed on the TMA slides. In addition to observing the subcellular localization of each LPAR, the expression level of each LPAR at each subcellular localization was recorded as final IHC score, calculated by IHC intensity score (0 to3) multiplied with IHC area score (0 to 3). A 2-sample t test was used to statistical analysis. Results: All three LPARs were widely distributed throughout human organs/tissues. All LPARs were expressed higher in nuclei than in cytoplasm. Nuclear expressed LPARs were all higher in overall malignant changes than in overall benign changes, which is especially true for nuclear expressed LPAR1 (LPAR1N): the IHC score for LPAR1N was 6.38 in overall malignant changes and 5.84 in overall benign changes (p = 0.016). The expression level of LPAR1 in nuclei or in cytoplasm is significantly (p<0.05) or obviously (p<0.09 and >0.05) different between benign and malignant changes in eight organs/tissues. The number of organs/tissues with such difference was five for LPAR2 and six for LPAR3. Hepatocellular carcinoma (HCC) had significantly higher expression level of LPAR1N (p = 0.000000001), LPAR2N (p = 0.00002) and LPAR3N (p = 0.00001) as compared with benign hepatic changes. The malignancies showed obviously alterations in expression level of two LPARs in three organs/tissues and one LPAR in eight organs/tissues. The malignancies in the rest organs/tissues, including breast and prostate showed no obvious difference between benign and malignant changes. Conclusions: This study is first to investigate systemic distribution of the LPAR1, LPAR2 and LPAR3 in benign and malignant changes throughout human organs/tissues. The results indicate that each LPAR has a unique expression pattern in a spectrum of organs/tissues. Differentially expressed LPARs between benign and malignant changes in different organs/tissues will help to understand the involvement of LPARs in the pathogenesis of cancer, and to find therapeutic targets in treatment of cancer. Citation Format: Andrew Bingham, Jinghe Mao, Chunyi Wang, Janice Lage, Xinchun Zhou. Differential expression of lysophosphatidic acid receptors (LPARs) between benign and malignant tissues in humans. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5003. doi:10.1158/1538-7445.AM2015-5003