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Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2002, Vol. 99, No. 5, pp. 1646-1650 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells Yao-Qi Huang, Jian-Jun Li, Liang Hu, Merlin Lee, and Simon Karpatkin From the Department of Medicine and Kaplan Cancer Center, New York University Medical School, New York, NY. Angiogenesis is required for tumor growth and metastasis. It has recently been suggested that thrombin is a potent promoter of angiogenesis. We therefore examined the possibility that thrombin could be inducing the expression of angiopoietin-2 (Ang-2), necessary for remodeling. Human umbilical vein endothelial cells were incubated with or without thrombin (1 U/mL) for 1 to 24 hours and then examined for messenger RNA (mRNA) by Northern analysis. Enhanced mRNA expression (about 4-fold over baseline) was noted at 4 hours. Enhanced expression of Ang-2 mRNA was secondary to enhanced transcription (about 4-fold), with no effect on stabilization. Enhanced Ang-2 mRNA transcription was inhibited by H7 and PD98059, indicating the requirement of serine/threonine kinases as well as the mitogen-activated protein kinase pathway. Up-regulation of mRNA was associated with enhanced Ang-2 protein synthesis and secretion as assayed by immunoblot. Thrombin-induced secreted Ang-2 inhibited the binding of recombinant 35S-Ang-1 to its Tie-2-Fc receptor, demonstrating functionality. Hirudin reversed this effect, demonstrating thrombin specificity. Thus, thrombin-induced tumorigenesis and metastasis is associated with enhanced Ang-2 protein synthesis and secretion via enhanced transcription of Ang-2. This could help explain how thrombin promotes angiogenesis. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Kumpers, J. Hellpap, S. David, R. Horn, H. Leitolf, H. Haller, and M. Haubitz Circulating angiopoietin-2 is a marker and potential mediator of endothelial cell detachment in ANCA-associated vasculitis with renal involvement Nephrol. Dial. Transplant., June 1, 2009; 24(6): 1845 - 1850. [Abstract] [Full Text] [PDF] K. L. Elzer, D. A. Heitzman, M. I. Chernin, and J. F. Novak Differential Effects of Serine Proteases on the Migration of Normal and Tumor Cells: Implications for Tumor Microenvironment Integr Cancer Ther, December 1, 2008; 7(4): 282 - 294. [Abstract] [PDF] D. Voskas, Y. Babichev, L. S. 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