Abstract
IntroductionLysophosphatidic acid (LPA) is a bioactive phospholipid with diverse effects on various cells. It interacts with at least three G-protein-coupled transmembrane receptors, namely LPA1, LPA2 and LPA3, whose expression in various tumours has not been fully characterized. In the present study we characterized the expression profile of LPA receptors in human breast cancer tissue and assessed the possible roles of each receptor.MethodsThe relative expression levels of each receptor's mRNA against β-actin mRNA was examined in surgically resected invasive ductal carcinomas and normal gland tissue using real-time RT-PCR. LPA2 expression was also examined immunohistochemically using a rat anti-LPA2 monoclonal antibody.ResultsIn 25 cases normal and cancer tissue contained LPA1 mRNA at similar levels, whereas the expression level of LPA2 mRNA was significantly increased in cancer tissue as compared with its normal counterpart (3479.0 ± 426.6 versus 1287.3 ± 466.8; P < 0.05). LPA3 was weakly expressed in both cancer and normal gland tissue. In 48 (57%) out of 84 cases, enhanced expression of LPA2 protein was confirmed in carcinoma cells as compared with normal mammary epithelium by immunohistochemistry. Over-expression of LPA2 was detected in 17 (45%) out of 38 premenopausal women, as compared with 31 (67%) out of 46 postmenopausal women, and the difference was statistically significant (P < 0.05).ConclusionThese findings suggest that upregulation of LPA2 may play a role in carcinogenesis, particularly in postmenopausal breast cancer.
Highlights
Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse effects on various cells
These findings suggest that upregulation of lysophosphatidic acid receptor 2 (LPA2) may play a role in carcinogenesis, in postmenopausal breast cancer
Patients and materials In the first part of the study, mRNA expression for each LPA receptor was evaluated in 25 cases of invasive ductal carcinoma, which were surgically resected in the Department of Surgery, University of Tokyo, from 1998 to 2003, and in six samples of adjacent normal gland tissue
Summary
Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse effects on various cells. It interacts with at least three G-protein-coupled transmembrane receptors, namely LPA1, LPA2 and LPA3, whose expression in various tumours has not been fully characterized. A high level of LPA has been detected in ascitic fluid from ovarian cancer patients [4,10,11]. These findings suggest that LPA may be a mediator of tumour development and progression [12]. In the same study the different phenotypes of knockout mice for each receptor suggested distinct roles for LPA1 and LPA2 in vivo
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