Des-gamma-carboxy prothrombin stimulates human vascular endothelial cell growth and migration.
Des-gamma-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.
Wang
Su-Bo
SB
School of Ocean Sciences, Shandong University at Weihai, 264209, Weihai, China.
Cheng
Yan-Na
YN
Cui
Shu-Xiang
SX
Zhong
Julia Li
JL
Ward
S G
SG
Sun
Li-Rui
LR
Chen
Ming-Hui
MH
Kokudo
Norihiro
N
Tang
Wei
W
Qu
Xian-Jun
XJ
D015415:Biomarkers; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007797:Laminin / Q000737:chemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011498:Protein Precursors / Q000494:pharmacology*; D011509:Proteoglycans / Q000737:chemistry; D011516:Prothrombin / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015415:Biomarkers; D004338:Drug Combinations; D007797:Laminin; D011498:Protein Precursors; D011509:Proteoglycans; D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; C008208:acarboxyprothrombin; D011516:Prothrombin; D003094:Collagen; D066246:ErbB Receptors; D020778:Matrix Metalloproteinase 2; C022616:thiazolyl blue