Identification of Stimulated Endothelial Cell-Binding Ligands Using In Vitro Phage Display
Date Issued
2005
Date
2005
Author(s)
Chang, Po-Chin
DOI
en-US
Abstract
Malignant tumor has become the most important cause of death around the world and in our country. Drug resistance formation due to high genetic instability of tumor cells were reported in conventional tumor therapies. Tumor progress and metastases depend on angiogenesis imply tumor vascular endothelial cells is a potent target of cancer therapy. Endothelial cells are stable in genetic mutations and inhibition of angiogenesis becomes hot research area. In this study, phage display was used to identify tumor vascular endothelial cells specific binding ligands. Angiostatin is a potent endogenous inhibitor of angiogenesis that specific bind to tumor vessels. Using phage-displayed peptide library, we have identified B-cell epitopes from several functional MAbs against angiostatin. These peptide ligands will be useful to identify the functional domain of angiostatin and develop anti-angiogenesis therapy. To identify peptide ligands specific binding to proliferated endothelial cells, phage display biopanning using VEGF stimulated HUVEC was performed. We have identified several peptide ligands with higher capability to bind stimulated-HUVEC. Some motifs of these peptide ligands have been published and some peptide ligands are novel. In vivo homing test showed that phage clone PCH118 targeting specifically to tumor tissue vasculature of oral cancer xenograft. Stimulated HUVEC-binding ligands identify in this study will be valuable to identify proliferated endothelial cell markers as well as develop targeted therapy.
Subjects
噬菌體顯現法
抗血管新生
標的性治療
血管內皮細胞標記
phage display
anti-angiogenesis
targeting therapy
vascular endothelial cell marker
SDGs
Type
other
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