Vascular Endothelial Growth Factor (VEGF) and Its Receptors in Tumor-Bearing Dogs

1999 ◽  
Vol 380 (12) ◽  
Author(s):  
Patrick Scheidegger ◽  
Wolfgang Weiglhofer ◽  
Stéphanie Suarez ◽  
Barbara Kaser-Hotz ◽  
Rudolf Steiner ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Tumor Bearing ◽  
Endothelial Growth Factor

Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 546-553 ◽  
Author(s):  
Hajime Kubo ◽  
Takashi Fujiwara ◽  
Lotta Jussila ◽  
Hiroyuki Hashi ◽  
Minetaro Ogawa ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Angiogenesis ◽  
Vascular Endothelial Cells ◽  
Lymphatic Vessels ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Endothelial Lining ◽  
Tumor Bearing ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) plays a major role in tumor angiogenesis. VEGF-C, however, is thought to stimulate the growth of lymphatic vessels because an expression of its specific receptor, VEGF receptor-3 (VEGFR-3), was demonstrated to be restricted to lymphatic vessels. Here we demonstrate that the inactivation of VEGFR-3 by a novel blocking monoclonal antibody (mAb) suppresses tumor growth by inhibiting the neo-angiogenesis of tumor-bearing tissues. Although VEGFR-3 is not expressed in adult blood vessels, it is induced in vascular endothelial cells of the tumor-bearing tissues. Hence, VEGFR-3 is another receptor tyrosine kinase involved in tumor-induced angiogenesis. Micro-hemorrhage in the tumor-bearing tissue was the most conspicuous histologic finding specific to AFL4 mAb-treated mice. Scanning microscopy demonstrated disruptions of the endothelial lining of the postcapillary venule, probably the cause of micro-hemorrhage and the subsequent collapse of the proximal vessels. These findings suggest the involvement of VEGFR-3 in maintaining the integrity of the endothelial lining during angiogenesis. Moreover, our results suggest that the VEGF-C/VEGFR-3 pathway may serve another candidate target for cancer therapy.

Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 546-553 ◽  
Author(s):  
Hajime Kubo ◽  
Takashi Fujiwara ◽  
Lotta Jussila ◽  
Hiroyuki Hashi ◽  
Minetaro Ogawa ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Angiogenesis ◽  
Vascular Endothelial Cells ◽  
Lymphatic Vessels ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Endothelial Lining ◽  
Tumor Bearing ◽  
Endothelial Growth Factor

Abstract Vascular endothelial growth factor (VEGF) plays a major role in tumor angiogenesis. VEGF-C, however, is thought to stimulate the growth of lymphatic vessels because an expression of its specific receptor, VEGF receptor-3 (VEGFR-3), was demonstrated to be restricted to lymphatic vessels. Here we demonstrate that the inactivation of VEGFR-3 by a novel blocking monoclonal antibody (mAb) suppresses tumor growth by inhibiting the neo-angiogenesis of tumor-bearing tissues. Although VEGFR-3 is not expressed in adult blood vessels, it is induced in vascular endothelial cells of the tumor-bearing tissues. Hence, VEGFR-3 is another receptor tyrosine kinase involved in tumor-induced angiogenesis. Micro-hemorrhage in the tumor-bearing tissue was the most conspicuous histologic finding specific to AFL4 mAb-treated mice. Scanning microscopy demonstrated disruptions of the endothelial lining of the postcapillary venule, probably the cause of micro-hemorrhage and the subsequent collapse of the proximal vessels. These findings suggest the involvement of VEGFR-3 in maintaining the integrity of the endothelial lining during angiogenesis. Moreover, our results suggest that the VEGF-C/VEGFR-3 pathway may serve another candidate target for cancer therapy.

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