Increased Tie2 expression, enhanced response to angiopoietin-1, and dysregulated angiopoietin-2 expression in hemangioma-derived endothelial cells.
نویسندگان
چکیده
Infantile hemangiomas are endothelial tumors that grow rapidly in the first year of life and regress slowly during early childhood. Although hemangiomas are well-known vascular lesions, little is known about the mechanisms that cause the excessive endothelial cell proliferation in these most common tumors of infancy. To investigate the molecular basis of hemangioma, we isolated endothelial cells from several proliferative-phase lesions and showed that these cells are clonal and exhibit abnormal properties in vitro (E. Boye, Y. Yu, G. Paranya, J. B. Mulliken, B. R. Olsen, J. Bischoff: Clonality and altered behavior of endothelial cells from hemangiomas. J Clin Invest 2001, 107:745-752). Here, we analyzed mRNA expression patterns of genes required for angiogenesis, including members of the vascular endothelial growth factor (VEGF)/VEGF receptor family and the angiopoietin/Tie family, in hemangioma-derived and normal endothelial cells. KDR, Flt-1, Tie1, Tie2, and angiopoietin-2 (Ang2) were strongly expressed in cultured hemangioma-derived endothelial cells and in hemangioma tissue. In contrast, there was little expression of angiopoietin-1 (Ang1) or VEGF. We found Tie2 mRNA and protein up-regulated with a concomitant increase in cellular responsiveness to Ang1 in most hemangioma-derived endothelial cells. Ang2 mRNA was down-regulated in response to serum in hemangioma-derived endothelial cells, but not in normal endothelial cells, suggesting altered regulation. These findings implicate Tie2 and its ligands Ang1 and Ang2 in the pathogenesis of hemangioma.
منابع مشابه
Enhancement of new vessel formation by angiopoietin-2/Tie2 signaling in endothelial progenitor cells: a new hope for future therapy?
The Tie2/angiopoietin pathway is crucial for angiogenesis, blood vessel maturation, and vascular endothelial integrity. The ligands for Tie2 are the angiopoietins, of which angiopoietin-1 (Ang1) and Ang2 have been the most studied. Suppression of plasma leakage, inhibition of vascular inflammation, and prevention of endothelial death are the three widely accepted vascular protective functions f...
متن کاملCyclical mechanical stretch enhances angiopoietin-2 and Tie2 receptor expression in cultured human umbilical vein endothelial cells.
Endothelial cells are essential for neovascularization. Angiopoietins and Tie receptors are required for a normal vasculature. How cyclical mechanical stretch affects the expression of components of the angiopoietin system is not known. In this study, we investigated the regulation of angiopoietins and Tie receptors by cyclical mechanical stretch in cultured human umbilical vein endothelial cel...
متن کاملEthanol stimulates endothelial cell angiogenic activity via a Notch- and angiopoietin-1-dependent pathway.
AIMS Our aims were to determine the effect of alcohol (EtOH) on endothelial angiogenic activity and to delineate the cell signalling mechanisms involved. METHODS AND RESULTS Treatment of human umbilical vein endothelial cells (HUVECs) with EtOH (1-100 mM, 24 h) dose-dependently increased their network formation on Matrigel (an index of angiogenesis) with a maximum response (2.5- to 3-fold inc...
متن کاملIsolation of Angiopoietin-1, a Ligand for the TIE2 Receptor, by Secretion-Trap Expression Cloning
TIE2 is a receptor-like tyrosine kinase expressed almost exclusively in endothelial cells and early hemopoietic cells and required for the normal development of vascular structures during embryogenesis. We report the identification of a secreted ligand for TIE2, termed Angiopoietin-1, using a novel expression cloning technique that involves intracellular trapping and detection of the ligand in ...
متن کاملRat aorta-derived mural precursor cells express the Tie2 receptor and respond directly to stimulation by angiopoietins.
Recent studies have implicated the Tie2 tyrosine-kinase receptor and its main ligands--angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2)--as crucial regulators of mural cell recruitment during angiogenesis. Angiopoietin-mediated activation of Tie2 promotes perivascular mural cell assembly, but the mechanisms regulating this process are poorly understood because differentiated mural cells do not...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The American journal of pathology
دوره 159 6 شماره
صفحات -
تاریخ انتشار 2001