Expression of Tie1, Tie2, and angiopoietins 1, 2, and 4 in Kaposi's sarcoma and cutaneous angiosarcoma.
The angiopoietins are recently described growth factors for vascular endothelium. The Tie1 and Tie2 receptors are expressed by endothelium. Acquired immune deficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS) and cutaneous angiosarcoma are malignancies of endothelial origin. KS involves primarily the skin and mucosal surfaces and is common in AIDS patients. In an effort to determine whether the angiopoietins and Tie receptors play a role in the pathobiology of angiosarcoma and KS, we studied the expression of angiopoietin-1, angiopoietin-2, angiopoietin-4, Tie1, and Tie2 mRNAs in biopsies of KS from 12 AIDS patients, in biopsies of cutaneous angiosarcoma from two patients, and in control biopsies of normal skin from three volunteers by in situ hybridization. Strong expression of angiopoietin-2, Tie1, and Tie2 mRNAs was detected in the tumor cells of KS and cutaneous angiosarcomas, in contrast to the focal low-level expression in normal skin biopsies. Focal low-level expression of angiopoietin-1 was seen in KS, cutaneous angiosarcomas, and in normal skin. Focal low-level expression of angiopoietin-4 was identified in a minority of KS lesions. These findings suggest that the angiopoietins and Tie receptors may play an important role in the pathobiology of KS and cutaneous angiosarcoma and identify additional potential targets for therapeutic intervention in these vascular malignancies.
Brown
L F
LF
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. lbrown@caregroup.harvard.edu
Dezube
B J
BJ
Tognazzi
K
K
Dvorak
H F
HF
Yancopoulos
G D
GD
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042682:Angiopoietins; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D006394:Hemangiosarcoma / Q000150:complications / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D042764:Receptors, TIE; D012016:Reference Values; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000378:metabolism*; D012878:Skin Neoplasms / Q000150:complications / Q000378:metabolism*
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042682:Angiopoietins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C105373:MEN1 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C118117:angiopoietin 4; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D042764:Receptors, TIE