Capillary Fenestration in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced Rat Bladder Carcinoma is Promoted by Vascular Endothelial Growth Factor.

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  • Wakui Shin
    Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato, Tokyo 105-8461 Japan
  • Muto Tomoko
    Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
  • Ohshige Hidetoshi
    Life Science Research Center, Lion Corporation, 100 Tajima, Odawara, Kanagawa 256-0811 Japan
  • Sasaki Shinji
    Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
  • Ogasawara Rie
    Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
  • Miyachi Syunsuke
    Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
  • Furusato Bungo
    Department of Pathology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku, Tokyo 160-0023 Japan
  • Takahashi Hiroyuki
    Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato, Tokyo 105-8461 Japan
  • Masaoka Toshio
    Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
  • Hano Hiroshi
    Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato, Tokyo 105-8461 Japan
  • Furusato Masakuni
    Department of Pathology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 Japan

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説明

Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein that specifically increases vascular permeability and stimulates angiogenesis. Recently we demonstrated a high level of VEGF and VEGF mRNA expression in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder carcinomas with abundant fenestrated capillaries. We speculated that the expression of VEGF might be involved in the induction or maintenance of capillary fenestration, and examined ultrastructurally the morphological alteration of blood capillaries in BBN-induced rat bladder carcinoma following the administration of neutralizing antibody against VEGF. Five minutes after administration, the fenestrated endothelial cell ratio and the number of fenestrae decreased significantly, and continued to decrease with time reaching a minimum at 10 minutes after administration. The ratio thereafter gradually increased and at 30 minutes returned to its control condition. These results showed the specific inhibition of VEGF bioactivity potently induced to close the capillary fenestrations. We can suggest that VEGF synthesized by BBN-induced rat bladder carcinoma cells specifically induces and maintains the tumor capillary fenestrations.

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