[Review Article]

Proteins Expressed on Tumor Endothelial Cells as Potential Targets for Anti-Angiogenic Therapy

Han-Chung Wu and Pi-Chun Li

Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan

Abstract:

The fact that solid tumors are dependent on blood supply has inspired many researchers to search for anti-angiogenic molecules that could be used therapeutically to halt the blood flow and rob tumors of nourishment and oxygen.  Some promising preclinical and clinical results further confirmed the advantages of angiogenesis inhibitors.  However, toxicity side effects and development of drug resistance in cancer cells have suggested the necessity to develop more specific and potent anti-angiogenic targets.  Tumor blood vessels express some molecules that are not present in resting blood vessels in normal tissues.  Many of these proteins, such as vascular endothelial growth factor receptor, integrins, delta-like ligand 4, EphB4, ephrin-B2, tumor endothelial markers 5 and 8, annexin A1 and fibronectin extra-domain B, are functionally important to tumor angiogenesis, and therefore can be taken as potential targets for anti-angiogenic therapy.  In this review article, we discuss these potential target proteins expressed on the tumor endothelial cells and their possible therapeutic use.

(Keywords: angiogenesis; tumor endothelial cells; tumor endothelial marker; VEGF)

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Received 3/17/08; Revised 3/27/08; Accepted 3/27/08.

1. Correspondence: Dr. Han-Chung Wu, Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Academia

Road Section 2, Nankang, Taipei 11529, Taiwan.  Phone: 886-2-27899528. E-mail: hcw0928@gate.sinica.edu.tw

2. Abbreviations: VEGF, vascular endothelial growth factor; PLGF, placenta-like growth factor; bFGF, basic fibroblast growth factor; PDGF, platelet-derived growth factor; Ang, angiopoietin; HIF-1a, hypoxia-inducible factor-1a; CEPs, circulating endothelial progenitor cells; PIGF, placenta growth factor; CECs, circulating endothelial cells; VEGFR, VEGF receptor; ECM, extracellular matrix; DLL4, delta-like ligand 4; TEMs, tumor endothelial markers; EDB, fibronectin extra-domain B.

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