Vascular endothelial growth factor-mediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype

S. Soker, Martin Kaefer, M. Johnson, M. Klagsbrun, A. Atala, M. R. Freeman

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF), which is often produced at high levels by tumor cells, is a well-known mediator of tumor angiogenesis. VEGF receptor tyrosine kinases, KDR/Flk-1 and Flt-1, have been thought to be expressed exclusively by endothelial cells. In this study, we have used a prostate tumor progression series comprised of a differentiated rat prostate epithelial cell line, NbE-1, and its highly motile clonal derivative, FB2. Injection of NbE-1 cells into the inferior vena cava of syngeneic rats indicated that these cells are nontumorigenic. Using the same model, FB2 cells generated rapidly growing and well-vascularized tumors in the lungs. NbE-1 expressed marginal levels of VEGF, whereas high levels of VEGF protein were detected in FB2-conditioned medium and in FB2 tumors in vivo. Analysis of 125I-VEGF165 binding to NbE-1 and FB2 cells indicated that only motile FB2 cells expressed the VEGF receptor Flt-1. Consistent with this finding, physiological concentrations of VEGF induced chemotactic migration in FB2 but not in NbE-1 cells. This is the first documentation of a functional Flt-1 receptor in prostate tumor cells. Our results suggest two roles for VEGF in tumor progression: a paracrine role as an angiogenic factor and a previously undescribed role as an autocrine mediator of tumor cell motility.

Original languageEnglish (US)
Pages (from-to)651-659
Number of pages9
JournalAmerican Journal of Pathology
Volume159
Issue number2
StatePublished - 2001
Externally publishedYes

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Vascular Endothelial Growth Factor A
Prostate
Phenotype
Neoplasms
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor
Angiogenesis Inducing Agents
Inferior Vena Cava
Conditioned Culture Medium
Documentation
Cell Movement
Endothelial Cells
Epithelial Cells
Cell Line
Lung
Injections
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Vascular endothelial growth factor-mediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype. / Soker, S.; Kaefer, Martin; Johnson, M.; Klagsbrun, M.; Atala, A.; Freeman, M. R.

In: American Journal of Pathology, Vol. 159, No. 2, 2001, p. 651-659.

Research output: Contribution to journalArticle

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