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Effect of PTK/ZK on the Angiogenic Switch in Head and Neck Tumors

¹ Angiogenesis Research Laboratory, and Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan School of Dentistry, 1011 N. University, Rm. 2309, Ann Arbor, MI 48109-1078, USA;
² Department of Stomatology, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil;
³ Department of Biomedical Engineering, University of Michigan College of Engineering; and
⁴ Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109-1078, USA

Correspondence: ^* corresponding author, jenor{at}umich.edu

Transformation of small avascular masses of tumor cells into rapidly progressive cancers is triggered by the angiogenic switch, a process that involves vascular endothelial growth factor (VEGF) signaling. We have shown that VEGF enhances the survival and angiogenic potential of endothelial cells by activating the Bcl-2-CXCL8 signaling axis. The purpose of this study was to evaluate the effect of a small-molecule inhibitor of VEGF receptors (PTK/ZK) on the initial stages of head and neck tumor angiogenesis. In vitro, PTK/ZK blocked head and neck tumor cell (OSCC3 or UM-SCC-17B)-induced Bcl-2 and CXCL8 expression in endothelial cells. Oral administration of PTK/ZK decreased xenograft head and neck tumor microvessel density, and inhibited Bcl-2 and CXCL8 expression in tumor-associated endothelial cells. Analysis of these data demonstrates that PTK/ZK blocks downstream targets of VEGF signaling in endothelial cells, and suggests that PTK/ZK may inhibit the angiogenic switch in head and neck tumors. Abbreviations: HDMEC, human dermal microvascular endothelial cells; VEGF, vascular endothelial growth factor; CXCL8, CXC ligand-8; PTK/ZK, PTK787/ZK222584.

Key Words: Neovascularization • angiogenesis • developmental therapeutics • cancer

Journal of Dental Research, Vol. 87, No. 12, 1166-1171 (2008)
DOI: 10.1177/154405910808701213


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