Abstract
Tumor growth beyond a size of 1-2 mm3 requires new blood supply to sustain the nutritional and oxygen demands of the proliferating cancer cells (1). Tumor neovascularization is a complex process involving endothelial cell proliferation, matrix degradation, endothelial cell migration and tube formation. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is an important angiogenic mediator secreted by tumor cells (2). VEGF binds to receptor tyrosine kinases flt-1 and KDR/flk-1, which are expressed primarily on endothelial cells. Receptor expression is increased under hypoxia, and recent studies suggest that VEGF itself can upregulate their levels on endothelial cells. In situ hybridization and immunocytochemical analyses have identified that VEGF receptors are overexpressed on the endothelial cells of intratumoral and peritumoral blood vessels. In contrast, blood vessels in the adjoining normal tissues showed almost undetectable levels of VEGF receptors (2). These results suggest that VEGF can be used to target toxin polypeptides to tumor vascular endothelium to inhibit angiogenesis. In this chapter, we will focus on VEGF-DT385 toxin conjugates prepared by chemical means, and we will describe methods to evaluate their biologic activity. Furthermore, a protocol is described to prepare VEGF-toxin fusion proteins.
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© 2001 Humana Press Inc., Totowa, NJ
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Ramakrishnan, S., Wild, R., Nojima, D. (2001). Targeting Tumor Vasculature Using VEGF-Toxin Conjugates. In: Hall, W.A. (eds) Immunotoxin Methods and Protocols. Methods in Molecular Biology™, vol 166. Humana Press. https://doi.org/10.1385/1-59259-114-0:219
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DOI: https://doi.org/10.1385/1-59259-114-0:219
Publisher Name: Humana Press
Print ISBN: 978-0-89603-775-5
Online ISBN: 978-1-59259-114-5
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