Lin, C.-I.C.-I.LinChen, C.-N.C.-N.ChenHuang, M.-T.M.-T.HuangLee, S.-J.S.-J.LeeLin, C.-H.C.-H.LinChang, C.-C.C.-C.ChangSHYH-JYE LEEHSINYU LEECHIUNG-NIEN CHEN2009-06-242018-07-062009-06-242018-07-062008http://ntur.lib.ntu.edu.tw//handle/246246/161475Lysophosphatidic acid (LPA) is a low-molecular-weight lipid growth factor, which binds to G-protein-coupled receptors. Previous studies have shown that LPA enhances vascular endothelial growth factor-A (VEGF-A) expression in cancer cells and promotes angiogenesis process. However, the roles of LPA in lymphatic vessel formation and lymphangiogenesis have not been investigated. Here, we demonstrated that LPA up-regulated VEGF-C mRNA and protein expressions in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression levels of lymphatic markers, including Prox-1, LYVE-1 and podoplanin, were enhanced in LPA-stimulated tube forming endothelial cells in vitro and in vivo. Moreover, we showed that pretreatment with MAZ51, a VEGFR-3 kinase inhibitor, and introduction of VEGFR-3 siRNA suppressed LPA-induced HUVEC tube formation and lymphatic marker expressions. These results demonstrated that LPA enhances expression of lymphatic markers through activating VEGF-C receptors in endothelial cells. This study provides basic information that LPA might be a target for therapeutics against lymphangiogenesis and tumor metastasis. ? 2008 Birkhaueser.application/pdf1566214 bytesapplication/pdfen-US[SDGs]SDG3biological marker; lysophosphatidic acid; messenger RNA; podoplanin; small interfering RNA; vasculotropin C; vasculotropin inhibitor; article; cell proliferation; cell stimulation; controlled study; endothelium cell; human; human cell; human tissue; in vitro study; in vivo study; protein expression; umbilical vein; upregulation; Biological Markers; Cell Proliferation; Cells, Cultured; Endothelial Cells; Homeodomain Proteins; Humans; Indoles; Lymphocytes; Lysophospholipids; Membrane Glycoproteins; Naphthalenes; RNA, Messenger; Tumor Suppressor Proteins; Up-Regulation; Vascular Endothelial Growth Factor C; Vesicular Transport Proteins10.1007/s00018-008-8314-9http://ntur.lib.ntu.edu.tw/bitstream/246246/161475/1/11.pdf