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Type: Journal article
Title: A potential autocrine role for vascular endothelial growth factor in prostate cancer
Author: Jackson, M.
Roberts, J.
Heckford, S.
Ricciardelli, C.
Stahl, J.
Horsfall, D.
Tilley, W.
Citation: Cancer Research, 2002; 62(3):854-859
Publisher: Amer Assoc Cancer Research
Issue Date: 2002
ISSN: 0008-5472
Statement of
Michael W. Jackson, James S. Roberts, Susan E. Heckford, Carmela Ricciardelli, Jurgen Stahl, David J. Horsfall and Wayne D. Tilley
Abstract: Vascular endothelial growth factor (VEGF) is a peptide growth factor specific for the tyrosine kinase receptors VEGF receptor-1 and -2 (VEGFR-1 and R-2). Whereas VEGF has well-defined actions on the vasculature, including the stimulation of endothelial cell growth and motility and blood vessel permeability, the function of the VEGF/ receptor pathway in other cell types is largely unknown. Recently, VEGFR-1 and R-2 expression has been reported in prostate tumor cells. In this study, we demonstrate that these receptors colocalize with VEGF in prostate tumor cells, prostatic intraepithelial neoplasia, and the basal cells of normal glands. Furthermore, in comparison with normal glands, the expression of VEGFR-1 and R-2 is increased in prostatic intraepithelial neoplasia and malignant cells in well and moderately differentiated prostate cancer but is decreased in poorly differentiated cancer. Culture of the prostate cancer cell line LNCaP in the presence of recombinant human VEGF165 resulted in a 50% increase in [3H]thymidine uptake by these cells and recruitment of quiescent cells into the cell cycle. This effect of recombinant human VEGF165 was abolished by neutralizing antisera to VEGFR-2. These data suggest that VEGF may not only mediate neovascularization associated with prostate cancer progression but may also directly stimulate prostate tumor cells via VEGFR-2-dependent autocrine and/or paracrine mechanisms.
Keywords: Tumor Cells, Cultured; Epithelial Cells; Humans; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Neovascularization, Pathologic; Receptor Protein-Tyrosine Kinases; Receptors, Vascular Endothelial Growth Factor; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors; Vascular Endothelial Growth Factor A; Endothelial Growth Factors; Receptors, Growth Factor; Proto-Oncogene Proteins; Recombinant Proteins; DNA, Neoplasm; Lymphokines; Immunoblotting; S Phase; Male
Rights: © 2002 American Association for Cancer Research
RMID: 0020020040
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Appears in Collections:Obstetrics and Gynaecology publications
Medicine publications

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