A murine vascular endothelial growth factor antibody inhibits in vivo growth of human Caki-I renal adenocarcinoma.
A number of studies have provided indirect evidence that angiogenesis is involved in tumour growth and metastasis formation of renal cell carcinoma (RCC). Nude mice bearing xenografts of human Caki-I RCC were treated i.p. for 3 weeks with a murine monoclonal antibody against vascular endothelial growth factor, VEGF (VEGF-ab). Tumour growth and mRNA expression of human and murine VEGF and murine VE-Cadherin in the tumours were measured. After 3 weeks of therapy, the tumour volume in the control nude mice was 548 +/- 98 mm3 compared to the tumours in the nude mice treated with VEGF-ab (122 +/- 24 mm3, p < 0.01). Treatment with VEGF-ab significantly reduced mRNA expression of murine VEGF-120 and murine VE-Cadherin (p < 0.05 and p < 0.01, respectively). The mRNA expression of human VEGF (hVEGF165, hVEGF189) and murine VEGF (mVEGF164) was unchanged due to antibody treatment. The mean percentage of apoptotic cells in tumours harvested from antibody-treated animals was significantly lower than in tumours from the control-treated animals (p < 0.02). These findings demonstrate for the first time that VEGF-ab significantly inhibit the growth of Caki-1 RCC in vivo.
Dagnaes-Hansen
F
F
Department of Medical Microbiology and Immunology, Bartholin Building, Wilheln Meyers Alle 240, University of Aarhus, DK-8000 Aarhus C, Denmark. nikrfdh@nednitro.au.dk
Rasmussen
L M
LM
Tilton
R
R
Denner
L
L
Flyvbjerg
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015703:Antigens, CD; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000556:secondary / Q000628:therapy*; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007680:Kidney Neoplasms / Q000473:pathology*; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D012878:Skin Neoplasms / Q000556:secondary; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D023041:Xenograft Model Antitumor Assays; D000099152:Cadherin 5
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015820:Cadherins; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099152:Cadherin 5