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Journals Cellular and Molecular Life Sciences Volume 65 Issue 17

C.-I. Lin C.-N. Chen M.-T. Huang S.-J. Lee C.-H. Lin C.-C. Chang H. Lee +8862-2363-6837 hsinyu@ntu.edu.tw Institute of Zoology National Taiwan University 1 Roosevelt Rd., Sec. 4 Taipei 106 Taiwan Department of Life Science National Taiwan University Taipei Taiwan Angiogenesis Research Center National Taiwan University Taipei Taiwan Department of Surgery National Taiwan University Hospital Taipei Taiwan Department of Pediatrics National Taiwan University Hospital Taipei Taiwan Laboratory of Molecular and Cellular Toxicology, Institute of Toxicology National Taiwan University Taipei Taiwan Division of Mechanics, Research Center for Applied Sciences Academia Sinica Taipei Taiwan 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.

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Lysophosphatidic acid up-regulates vascular endothelial growth factor-C and lymphatic marker expressions in human endothelial cells

More Info
  • Publisher Birkhäuser-Verlag
  • Copyright Copyright © 2008 by Birkhaueser
  • Subject Life Sciences; Cell Biology; Biomedicine general; Life Sciences, general; Biochemistry, general
  • ISSN 1420-682X
  • eISSN 1420-9071
  • D.O.I. 10.1007/s00018-008-8314-9
  • Publisher site Get PDF  

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