Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / therapeutic use*
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Antigens, CD
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Apoptosis / drug effects
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Cadherins / biosynthesis
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Cadherins / genetics
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Carcinoma, Renal Cell / secondary
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Carcinoma, Renal Cell / therapy*
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Endothelial Growth Factors / antagonists & inhibitors
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Endothelial Growth Factors / biosynthesis
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Endothelial Growth Factors / genetics
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Endothelial Growth Factors / immunology*
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Immunotherapy*
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Intercellular Signaling Peptides and Proteins / biosynthesis
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / immunology*
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Kidney Neoplasms / pathology*
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Lymphokines / antagonists & inhibitors
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Lymphokines / biosynthesis
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Lymphokines / genetics
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Lymphokines / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / immunology*
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Neoplasm / biosynthesis
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RNA, Neoplasm / genetics
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Skin Neoplasms / secondary
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Xenograft Model Antitumor Assays
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Cadherins
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Endothelial Growth Factors
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Intercellular Signaling Peptides and Proteins
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Lymphokines
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Neoplasm Proteins
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RNA, Messenger
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RNA, Neoplasm
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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cadherin 5