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

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Abstract

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.

Original languageEnglish
Pages (from-to)160-165
Number of pages6
JournalInternational Journal of Cancer
Volume117
Issue number1
DOIs
Publication statusPublished - Oct 20 2005

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Liver Neoplasms
Pancreatic Neoplasms
Nude Mice
Neoplasm Metastasis
Injections
Liver
Hepatocyte Growth Factor
Kringles
Neoplasms
Angiogenesis Inhibitors
Growth
Microvessels
Adenoviridae
Necrosis
Therapeutics
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Suppression of metastasis of human pancreatic cancer to the liver by transportal injection of recombinant adenoviral NK4 in nude mice. / Murakami, Mitsuhiko; Nagai, Eishi; Mizumoto, Kazuhiro; Saimura, Michiyo; Ohuchida, Kenoki; Inadome, Naoki; Matsumoto, Kunio; Nakamura, Toshikazu; Maemondo, Makoto; Nukiwa, Toshihiro; Tanaka, Masao.

In: International Journal of Cancer, Vol. 117, No. 1, 20.10.2005, p. 160-165.

Research output: Contribution to journalArticle

Murakami, M, Nagai, E, Mizumoto, K, Saimura, M, Ohuchida, K, Inadome, N, Matsumoto, K, Nakamura, T, Maemondo, M, Nukiwa, T & Tanaka, M 2005, 'Suppression of metastasis of human pancreatic cancer to the liver by transportal injection of recombinant adenoviral NK4 in nude mice', International Journal of Cancer, vol. 117, no. 1, pp. 160-165. https://doi.org/10.1002/ijc.21143
Murakami, Mitsuhiko ; Nagai, Eishi ; Mizumoto, Kazuhiro ; Saimura, Michiyo ; Ohuchida, Kenoki ; Inadome, Naoki ; Matsumoto, Kunio ; Nakamura, Toshikazu ; Maemondo, Makoto ; Nukiwa, Toshihiro ; Tanaka, Masao. / Suppression of metastasis of human pancreatic cancer to the liver by transportal injection of recombinant adenoviral NK4 in nude mice. In: International Journal of Cancer. 2005 ; Vol. 117, No. 1. pp. 160-165.
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