Vascular endothelial growth factor (VEGF) and its receptors in tumor-bearing dogs.
The molecular biology of the angiogenic growth factor, vascular endothelial growth factor (VEGF), has been studied in the dog. All major isoforms of VEGF are present in the dog. The amino acid sequences are identical between human and dog in the loop regions that are responsible for receptor binding. Accordingly, the VEGF receptors of dogs and humans are very similar and permit functional exchange of the growth factor. Here we show that canine VEGF activates human endothelial cells to the same extent as human VEGF. Similarly, the two proteins display identical cell binding properties. The VEGF receptor 1 (Flt-1) shows the same alternative splicing in humans and dogs and is overexpressed in the majority of tumors in both species. VEGF occurs also in canine tumors in similar relative quantities as in human malignancies. Based on the literature and our study we suggest that the molecular biology and the function of the VEGF signaling system are virtually identical in humans and canines and in healthy as well as in disease conditions.
Scheidegger
P
P
Institute of Medical Radiobiology of the University of Zurich and the Paul Scherrer Institute, Villigen PSI, Switzerland.
Weiglhofer
W
W
Suarez
S
S
Kaser-Hotz
B
B
Steiner
R
R
Ballmer-Hofer
K
K
Jaussi
R
R
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D004285:Dogs; D016228:Endothelial Growth Factors / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008222:Lymphokines / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1