The temporal-spatial expression of VEGF, angiopoietins-1 and 2, and Tie-2 during tumor angiogenesis and their functional correlation with tumor neovascular architecture.
Angiopoietins play a pivotal role in tumor angiogenesis by modulating vascular endothelial proliferation and survival. The expression of angiopoietins 1 and 2 (Ang-1 and Ang-2) and vascular endothelial growth factor (VEGF) has been documented in human malignant glioma. The expression of Ang-1, Ang-2, VEGF, and Tie-2, a member of the receptor tyrosine kinases and the natural receptor for both Ang-1 and Ang-2, follows a distinct transcriptional profile in vivo. Ang-2 and VEGF were expressed early in tumor formation and their levels increased throughout tumor growth. Their expression coincided with the expansion of the tumor mass and the formation of the vascular tree. There was no significant change in the expression of Tie-2 and Ang-1. The expression of Ang-1 and Tie-2 was more noticeable at the periphery of the tumor. The expression of Ang-2 was more robust at the periphery and within the tumor mass, and VEGF was more concentrated within the center of the tumor. This distinct expression profile may explain the morphology of the newly formed vessels at various times and regions of the tumor. The lack of concomitant expression of Ang-1 may underscore the unopposed endovascular induction by Ang-2 and VEGF resulting in the chaotic appearance and fragility of tumor vessels.
Department of Neurosurgery, Stanford Medical School, Stanford, CA, USA. vkt@stanford.edu
Victor
V
Tse
Lei
L
Xu
Yun C
YC
Yung
Justin G
JG
Santarelli
David
D
Juan
Klaus
K
Fabel
Gerald
G
Silverberg
Griffith
G
Harsh
D042683:Angiopoietin-1 / Q000096:biosynthesis* / Q000235:genetics; D042702:Angiopoietin-2 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D042787:Receptor, TIE-2 / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2