Lysophosphatidic acid stimulates the proliferation and motility of malignant pleural mesothelioma cells through lysophosphatidic acid receptors, LPA1 and LPA2.
نویسندگان
چکیده
Lysophosphatidic acid (LPA) is one of the simplest natural phospholipids. This phospholipid is recognized as an extracellular potent lipid mediator with diverse effects on various cells. Although LPA is shown to stimulate proliferation and motility via LPA receptors, LPA(1) and LPA(2), in several cancer cell lines, the role of LPA and LPA receptors for malignant pleural mesothelioma (MPM) has been unknown. MPM is an aggressive malignancy with a poor prognosis and the incidence is increasing and is expected to increase further for another 10-20 years worldwide. Therefore, the development of novel effective therapies is needed urgently. In this study, we investigated the effect of LPA on the proliferation and motility of MPM cells. We found that all 12 cell lines and four clinical samples of MPM expressed LPA(1), and some of them expressed LPA(2), LPA(3), LPA(4) and LPA(5). LPA stimulated the proliferation and motility of MPM cells in a dose-dependent manner. Moreover, LPA-induced proliferation was inhibited by Ki16425, an inhibitor of LPA(1), and small interfering RNA against LPA(1), but not LPA(2). Interestingly, LPA-induced motility was inhibited by small interfering RNA against LPA(2), but not LPA(1), unlike a number of previous reports. These results indicate that LPA is a critical factor on proliferation though LPA(1), and on motility though LPA(2) in MPM cells. Therefore, LPA and LPA receptors, LPA(2) as well as LPA(1), represent potential therapeutic targets for patients with MPM.
منابع مشابه
Lysophosphatidic acid receptors determine tumorigenicity and aggressiveness of ovarian cancer cells.
BACKGROUND Lysophosphatidic acid (LPA) acts through the cell surface G protein-coupled receptors, LPA1, LPA2, or LPA3, to elicit a wide range of cellular responses. It is present at high levels in intraperitoneal effusions of human ovarian cancer increasing cell survival, proliferation, and motility as well as stimulating production of neovascularizing factors. LPA2 and LPA3 and enzymes regulat...
متن کاملLPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells.
Lysophosphatidic acid (LPA) acts via binding to specific G protein-coupled receptors and has been implicated in the biology of breast cancer. Here, we characterize LPA receptor expression patterns in common established breast cancer cell lines and their contribution to breast cancer cell motility. By measuring expression of the LPA receptors LPA1, LPA2, and LPA3 with real-time quantitative PCR,...
متن کاملAutotaxin and LPA Receptors Represent Potential Molecular Targets for the Radiosensitization of Murine Glioma through Effects on Tumor Vasculature
Despite wide margins and high dose irradiation, unresectable malignant glioma (MG) is less responsive to radiation and is uniformly fatal. We previously found that cytosolic phospholipase A2 (cPLA(2)) is a molecular target for radiosensitizing cancer through the vascular endothelium. Autotaxin (ATX) and lysophosphatidic acid (LPA) receptors are downstream from cPLA(2) and highly expressed in MG...
متن کاملRole of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma
BACKGROUND Lysophosphatidic acid (LPA) plays a critical role in airway inflammation through G protein-coupled LPA receptors (LPA1-3). We have demonstrated that LPA induced cytokine and lipid mediator release in human bronchial epithelial cells. Here we provide evidence for the role of LPA and LPA receptors in Th2-dominant airway inflammation. METHODS Wild type, LPA1 heterozygous knockout mice...
متن کاملNo Mutations of Lysophosphatidic Acid Receptor Genes in Lung Adenocarcinomas Induced by N-Nitrosobis(2-hydroxypropyl)amine in Rats
Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation and migration, and protects cells from apoptosis. It interacts with specific G protein-coupled transmembrane receptors. Recently, frequent mutations of the LPA receptor-1 (LPA1) gene were detected in rat lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP). In this study, to evaluate t...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer science
دوره 99 8 شماره
صفحات -
تاریخ انتشار 2008