Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2 (KDR/Flk-1) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice

R. A. Brekken, J. P. Overholser, V. A. Stastny, J. Waltenberger, J. D. Minna, P. E. Thorpe

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Abstract

Vascular endothelial growth factor (VEGF) is a multifunctional angiogenic growth factor that is a primary stimulant of the development and maintenance of a vascular network in embryogenesis and the vascularization of solid tumors. At the present time there are two well-characterized receptors for VEGF that are selectively expressed on endothelium. VEGF receptor 2 [VEGFR2 (KDR/FIk-1)] mediates endothelial cell mito-genesis and permeability increases, whereas the role of VEGF receptor 1 [VEGFR1 (Flt-1)] has not been clearly defined. In the present study, a monoclonal antibody, 2C3, is shown to block the interaction of VEGF with VEGFR2 but not with VEGFR1 through ELISA, receptor binding assays, and receptor activation assays. 2C3 blocks the VEGF-induced vascular permeability increase in guinea pig skin. 2C3 has potent antitumor activity, inhibiting the growth of newly injected and established human tumor xenografts in mice. These findings demonstrate the usefulness of 2C3 in dissecting the pathways that are activated by VEGF in cells that express both VEGFR1 and VEGFR2, as well as highlighting the dominant role of VEGFR2 in mediating VEGF-induced vascular permeability increases and tumor angiogenesis.

Original languageEnglish (US)
Pages (from-to)5117-5124
Number of pages8
JournalCancer Research
Volume60
Issue number18
StatePublished - Sep 15 2000

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Neoplasm Antibodies
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor A
Growth
Capillary Permeability
Vascular Endothelial Growth Factor Receptor-1
Neoplasms
Vascular Endothelial Growth Factor Receptor
Angiogenesis Inducing Agents
Heterografts
Endothelium
Embryonic Development
Blood Vessels
Permeability
Intercellular Signaling Peptides and Proteins
Guinea Pigs
Endothelial Cells
Enzyme-Linked Immunosorbent Assay
Monoclonal Antibodies
Maintenance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2 (KDR/Flk-1) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice. / Brekken, R. A.; Overholser, J. P.; Stastny, V. A.; Waltenberger, J.; Minna, J. D.; Thorpe, P. E.

In: Cancer Research, Vol. 60, No. 18, 15.09.2000, p. 5117-5124.

Research output: Contribution to journalArticle

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AU - Overholser, J. P.

AU - Stastny, V. A.

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AU - Minna, J. D.

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