Lysophosphatidic acid up-regulates vascular endothelial growth factor-C and lymphatic marker expressions in human endothelial cells
Resource
Cellular and Molecular Life Sciences 65 (17): 2740-2751
Journal
Cellular and Molecular Life Sciences
Pages
2740-2751
Date Issued
2008
Date
2008
Author(s)
Lin, C.-I.
Chen, C.-N.
Huang, M.-T.
Lee, S.-J.
Lin, C.-H.
Chang, C.-C.
Abstract
Lysophosphatidic 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.
SDGs
Other Subjects
biological 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 Proteins
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