Suppression of metastasis of human pancreatic cancer to the liver by transportal injection of recombinant adenoviral NK4 in nude mice

Mitsuhiko Murakami, Eishi Nagai, Kazuhiro Mizumoto, Michiyo Saimura, Kenoki Ohuchida, Naoki Inadome, Kunio Matsumoto, Toshikazu Nakamura, Makoto Maemondo, Toshihiro Nukiwa, Masao Tanaka

研究成果: Contribution to journalArticle査読

25 被引用数 (Scopus)

抄録

NK4, a 4-kringle fragment of hepatocyte growth factor (HGF), is an HGF antagonist that also acts as an angiogenesis inhibitor. NK4 strongly inhibits the infiltration, metastasis, and tumor growth of pancreatic cancer. The aim of our study was to evaluate the antitumor effect of adenovirus-mediated NK4 gene transfer to the liver on hepatic metastasis of pancreatic cancer in vivo. We constructed recombinant adenoviral NK4 (Ad-NK4), which encodes a secreted form of human NK4. Intrasplenic injection of Ad-NK4 induced high and relatively maintained expression of NK4 protein in the liver and suppressed the number and growth of metastatic foci in the liver in a nude mouse model. Microscopically, central necrosis was found even in small metastatic foci in Ad-NK4 treated mice. Immunohistochemical analysis of metastatic tumors showed a remarkable decrease in microvessel density and an increase in the number of apoptotic tumor cells after treatment with Ad-NK4. These results indicate that intraportal injection of Ad-NK4 may be a useful therapeutic modality for the clinical control of hepatic metastasis in pancreatic cancer.

本文言語英語
ページ(範囲)160-165
ページ数6
ジャーナルInternational Journal of Cancer
117
1
DOI
出版ステータス出版済み - 10 20 2005

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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