期刊
BLOOD
卷 99, 期 5, 页码 1646-1650出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.V99.5.1646
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- NHLBI NIH HHS [HL-13336-28] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL013336] Funding Source: NIH RePORTER
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 base-line) 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 Wand 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 S-35-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. (C) 2002 by The American Society of Hematology.
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