Open AccessLysophosphatidic acid stimulates the proliferation and motility of malignant pleural mesothelioma cells through lysophosphatidic acid receptors, LPA 1 and LPA 2
Author(s) -
Yamada Tadaaki,
Yano Seiji,
Ogino Hirokazu,
Ikuta Kenji,
Kakiuchi Soji,
Hanibuchi Masaki,
Kanematsu Takanori,
Taniguchi Tetsuo,
Sekido Yoshitaka,
Sone Saburo
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00848.x
Subject(s) - lysophosphatidic acid , autotaxin , motility , small interfering rna , cell growth , receptor , cell migration , cancer research , biology , cell culture , microbiology and biotechnology , cell , chemistry , transfection , biochemistry , genetics
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. ( Cancer Sci 2008; 99: 1603–1610)