, Volume 13, Issue 8, pp 1145-1155
Date: 21 Jun 2006

Selective Blockade of Vascular Endothelial Growth Factor Receptor 2 With an Antibody Against Tumor-Derived Vascular Endothelial Growth Factor Controls the Growth of Human Pancreatic Adenocarcinoma Xenografts

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Abstract

Background

Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, is critical for growth of human pancreatic adenocarcinoma. Preclinical studies demonstrate that blockade of VEGF activity can control the growth of pancreatic tumors in mice. In this study, we evaluated the efficacy of 2C3, an antibody that inhibits VEGF receptor 2 activation by human VEGF, to inhibit the growth of human pancreatic adenocarcinoma in mice.

Methods

Human pancreatic cancer cell lines (MiaPaca-2, Panc-1, and Capan-1) were used to establish xenografts in nu/nu mice. The expression of VEGF and its receptors was determined in each cell line. Proliferation of tumor cells in vitro and tumor growth in vivo in the presence of 2C3 or a control antibody was evaluated. The effect of 2C3 on tumor weight, total vessel density, number of pericyte-associated vessels, and tumor perfusion was determined, and the level of 2C3 in the serum of animals was measured by enzyme-linked immunosorbent assay.

Results

2C3 did not affect the proliferation of cells in culture. 2C3 was present and active in the serum of tumor-bearing animals treated with 2C3, and these animals showed a decrease in tumor burden compared with control-treated mice. Therapy with 2C3 resulted in reduced vascular function, measured by a decrease in vessel density and in the percentage of vessels associated with pericytes. Furthermore, tumors derived from Capan-1 cells demonstrated decreased perfusion after treatment with 2C3.

Conclusions

Blockade of VEGF receptor 2 activation by tumor-derived VEGF decreases tumor vessel function and growth of some human pancreatic adenocarcinoma cell lines in mice.

Presented at the 57th Annual Meeting of the Society of Surgical Oncology, New York, New York, March 2004.
Dr. Brekken is a paid consultant for, receives research support through a sponsored research agreement with, and has an equity interest in Peregrine Pharmaceuticals Inc., a company that has licensed the exclusive rights to 2C3 from the University of Texas.