Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice

Michiyo Saimura, Eishi Nagai, Kazuhiro Mizumoto, Naoki Maehara, Hidenobu Okino, Mitsuo Katano, Kunio Matsumoto, Toshikazu Nakamura, Kou Narumi, Toshihiro Nukiwa, Masao Tanaka

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Abstract

NK4, composed of the N-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts not only as a competitive antagonist for HGF but also as a potent angiogenesis inhibitor. This study was designed to assess a therapeutic potential of adenovirus-mediated NK4 gene transfer for disseminated pancreatic cancer cells in the peritoneal lavage of nude mice. We constructed a recombinant adenovirus NK4 (Ad-NK4), which encodes a secretable form of human NK4. In vitro migration of AsPC-1 (human pancreatic cancer cell line) was stimulated by HGF, and it was completely inhibited by Ad-NK4 transfection. Weekly intraperitoneal injections of Ad-NK4 could suppress the development of tumor nodules in a nude mouse peritoneal dissemination model. NK4 expression was detected in the disseminated nodules, liver, pancreas, spleen, and mesenterium. Immunohistochemical study of the disseminated tumors showed a remarkable decrease in microvessel density and an increase in number of apoptotic tumor cells in the Ad-NK4-treated mice. Survival of the Ad-NK4-treated mice was significantly improved. This study indicates that the intraperitoneal transduction of adenovirus- mediated NK4 gene may be a useful therapeutic modality to prevent the development of peritoneal dissemination of pancreatic cancer.

Original languageEnglish
Pages (from-to)799-806
Number of pages8
JournalCancer Gene Therapy
Volume9
Issue number10
DOIs
Publication statusPublished - Jan 1 2002

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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