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Pancreatic cancer cell‐derived vascular endothelial growth factor is biologically active in vitro and enhances tumorigenicity in vivo
Author(s) -
Luo Jianying,
Guo Ping,
Matsuda Kei,
Truong Nhan,
Lee Annie,
Chun Carlene,
Cheng ShiYuan,
Korc Murray
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1202
Subject(s) - pancreatic cancer , vascular endothelial growth factor , cancer research , in vivo , angiogenesis , cell growth , biology , pancreatic disease , cell culture , in vitro , adenocarcinoma , cancer , endocrinology , medicine , pancreas , vegf receptors , biochemistry , genetics , microbiology and biotechnology
Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator that acts by binding to high‐affinity transmembrane receptors. Although both VEGF and its receptors are overexpressed in human pancreatic ductal adenocarcinoma (PDAC), this malignancy is not generally considered to be highly vascular. It is not known, therefore, whether the abundance of VEGF in PDAC is biologically relevant. To address this issue, we measured the angiogenic effects of pancreatic cancer cell‐derived VEGF in an in vitro endothelial cell proliferation assay and characterized the consequences of suppressing VEGF expression on pancreatic tumor growth in an athymic nude mouse model. We found that human pancreatic cancer cell lines secrete large quantities of biologically active VEGF into conditioned medium (CM). Stable transfection of an anti‐sense VEGF 189 (AS‐VEGF 189 ) expression construct into PANC‐1 pancreatic cancer cells resulted in decreased VEGF expression and secretion, a decreased capacity of the resultant CM to enhance endothelial cell proliferation and a significant attenuation of tumor cell proliferation in vitro . Furthermore, when injected into athymic nude mice, AS‐VEGF 189 ‐expressing cells exhibited an 80% decrease in tumor growth compared with control cells. These results support the hypothesis that VEGF promotes pancreatic cancer growth in vivo and suggest that anti‐VEGF therapy may be useful in the treatment of this disease. © 2001 Wiley‐Liss, Inc.