Des-gamma-carboxyl prothrombin-promoted vascular endothelial cell proliferation and migration.
Des-gamma-carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma. Previously, we have demonstrated that DCP stimulates cell proliferation in hepatocellular carcinoma cell lines through Met-Janus kinase 1 signal transducer and activator of transcription 3 signaling pathway. In the present study, we demonstrated that DCP induces both cell proliferation and migration in human umbilical vein endothelial cells. DCP was found to bind with the kinase insert domain receptor (KDR), alternatively referred to as vascular endothelial growth factor receptor-2. Furthermore, DCP induced autophosphorylation of KDR and its downstream effector phospholipase C-gamma and mitogen-activated protein kinase (MAPK). To support these results, we showed that DCP-induced cell proliferation and cell migration were inhibited by KDR short interfering RNA, KDR kinase inhibitor, or MAPK inhibitor. In conclusion, these results indicate that DCP is a novel type of vascular endothelial growth factor that possesses potent mitogenic and migrative activities.
Fujikawa
Tatsuya
T
Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Shiraha
Hidenori
H
Ueda
Naoki
N
Takaoka
Nobuyuki
N
Nakanishi
Yutaka
Y
Matsuo
Noriyuki
N
Tanaka
Shigetomi
S
Nishina
Shin-ichi
S
Suzuki
Mayumi
M
Takaki
Akinobu
A
Sakaguchi
Kohsaku
K
Shiratori
Yasushi
Y
D015415:Biomarkers / Q000737:chemistry*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D020868:Gene Silencing; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D011498:Protein Precursors / Q000737:chemistry*; D011516:Prothrombin / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D015415:Biomarkers; D011498:Protein Precursors; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C008208:acarboxyprothrombin; D011516:Prothrombin; D053613:Janus Kinase 1; D051966:Phospholipase C gamma