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Vascular Endothelial Growth Factor (VEGF)-C Differentially Affects Tumor Vascular Function and Leukocyte Recruitment: Role of VEGF-Receptor 2 and Host VEGF-A 1

 Ananth Kadambi  ;  Carla Mouta Carreira  ;  Chae-ok Yun  ;  Timothy P. Padera  ;  Dennis E. J. G. J. Dolmans  ;  Peter Carmeliet  ;  Dai Fukumura  ;  Rakesh K. Jain 
 CANCER RESEARCH, Vol.61(6) : 2404-2408, 2001 
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Animals ; Capillary Permeability/physiology ; Cell Communication/physiology ; Cell Division/physiology ; Endothelial Growth Factors/biosynthesis ; Endothelial Growth Factors/genetics ; Endothelial Growth Factors/physiology* ; Endothelium, Vascular/pathology ; Leukocytes/pathology* ; Mice ; Mice, SCID ; Neoplasms, Experimental/blood supply* ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/physiopathology* ; RNA/biosynthesis ; RNA/genetics ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors ; Receptor Protein-Tyrosine Kinases/physiology* ; Receptors, Growth Factor/antagonists & inhibitors ; Receptors, Growth Factor/physiology* ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C
Unlike vascular endothelial growth factor (VEGF)-A, the effect of VEGF-C on tumor angiogenesis, vascular permeability, and leukocyte recruitment is not known. To this end, we quantified in vivo growth and vascular function in tumors derived from two VEGF-C-overexpressing (VC+) and mock-transfected cell lines (T241 fibrosarcoma and VEGF-A−/− embryonic stem cells) grown in murine dorsal skinfold chambers. VC+ tumors grew more rapidly than mock-transfected tumors and exhibited parallel increases in tumor angiogenesis. Furthermore, VEGF-C overexpression elevated vascular permeability in T241 tumors, but not in VEGF-A−/− tumors. Surprisingly, unlike VEGF-A, VEGF-C did not increase leukocyte rolling or adhesion in tumor vessels. Administration of VEGF receptor (VEGFR)-2 neutralizing antibody DC101 reduced vascular density and permeability of both VC+ and mock-transduced T241 tumors. These data suggest that VEGFR-2 signaling is critical for tumor angiogenesis and vascular permeability and that VEGFR-3 signaling does not compensate for VEGFR-2 blockade. An alternate VEGFR, VEGFR-1 or neuropilin-1, may modulate adhesion of leukocytes to tumor vessels.
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5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
Yonsei Authors
Yun, Chae Ok(윤채옥)
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