Des-γ-carboxy prothrombin stimulates human vascular endothelial cell growth and migration |
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Authors: | Su-Bo Wang Yan-Na Cheng Shu-Xiang Cui Julia Li Zhong S. G. Ward Li-Rui Sun Ming-Hui Chen Norihiro Kokudo Wei Tang Xian-Jun Qu |
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Affiliation: | (1) School of Ocean Sciences, Shandong University at Weihai, 264209 Weihai, China;(2) Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 250012 Jinan, China;(3) Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, 250062 Jinan, China;(4) Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2, 7AV, UK;(5) Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 113-8655, Japan |
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Abstract: | Des-γ-carboxy prothrombin (DCP) is an aberrant prothrombin produced by hepatocellular carcinoma (HCC) cells. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. However, the role of DCP in the development of angiogenesis is not well understood. Herein, we report the effects of DCP on growth and migration of human vascular endothelial cells. DCP significantly stimulated the proliferation of HUVEC (ECV304) cells in a dose and time dependent manner, as measured by the MTT assay. A continuous rapid migration of ECV304 cells was observed in the presence of DCP measured by the scratch wound assay. The continuous rapid invasive activity, measured by transwell chamber assay also showed that DCP increased endothelial cells migration through the reconstituted extracellular matrix (Matrigel). Further, the tube formation of vascular endothelial cells on 3-D Matrigel showed an increased number of branch points of ECV304 cells induced by DCP in a dose dependent manner. The levels of vascular endothelial cell growth-related angiogenic factors and matrix metalloproteinase were also examined. DCP significantly stimulated the expression levels of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 (latent and active). Together, these data suggest that DCP is a novel type of vascular endothelial growth factor that possesses potent mitogenic and migrative activities in angiogenesis of HCC. S. Cui and X.-J. Qu contributed equally to this work. |
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Keywords: | HCC DCP Human vascular endothelial cell Angiogenesis EGFR VEGF MMP-2 |
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