Gene transduction of NK4, HGF antagonist, inhibits in vitro invasion and in vivo growth of human pancreatic cancer

Naoki Maehara, Eishi Nagai, Kazuhiro Mizumoto, Norihiro Sato, Kunio Matsumoto, Toshikazu Nakamura, Ko Narumi, Toshihiro Nukiwa, Masao Tanaka

Research output: Contribution to journalArticle

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Abstract

In this study, we investigated the therapeutic effects of adenovirally-mediated transfer of the sequence of NK4, an antagonist for hepatocyte growth factor (HGF), against human pancreatic carcinoma. HGF has been implicated to play an important role in invasion and metastasis of various human cancers through tumor-stromal interactions. Although NK4 has been shown to block the metastatic behavior of cancer cells, problems with cellular delivery of NK4 must be addressed before it can be used for clinical trials. The effects of NK4 gene transduction mediated by recombinant adenovirus (Ad-NK4) were evaluated in a human pancreatic cancer cell line (SUIT-2) by in vitro scattering assays, invasion assays, and subcutaneous transplantation in nude mice. NK4 transduction markedly inhibited scattering and invasion of SUIT-2 cells stimulated by HGF without affecting cell proliferation in vitro. Furthermore, Ad-NK4 significantly inhibited the growth of tumors transplanted to nude mice. The tumor reduction induced by Ad-NK4 was associated with a decreased number of blood vessels surrounding the tumors. These findings suggest that Ad-NK4 gene therapy may be a unique and promising strategy for the treatment of pancreatic cancer.

Original languageEnglish
Pages (from-to)417-426
Number of pages10
JournalClinical and Experimental Metastasis
Volume19
Issue number5
DOIs
Publication statusPublished - Aug 23 2002

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Hepatocyte Growth Factor
Pancreatic Neoplasms
Growth
Genes
Neoplasms
Nude Mice
Vascular Tissue Neoplasms
Therapeutic Uses
Adenoviridae
Genetic Therapy
Transplantation
Cell Proliferation
In Vitro Techniques
Clinical Trials
Neoplasm Metastasis
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Gene transduction of NK4, HGF antagonist, inhibits in vitro invasion and in vivo growth of human pancreatic cancer. / Maehara, Naoki; Nagai, Eishi; Mizumoto, Kazuhiro; Sato, Norihiro; Matsumoto, Kunio; Nakamura, Toshikazu; Narumi, Ko; Nukiwa, Toshihiro; Tanaka, Masao.

In: Clinical and Experimental Metastasis, Vol. 19, No. 5, 23.08.2002, p. 417-426.

Research output: Contribution to journalArticle

Maehara, Naoki ; Nagai, Eishi ; Mizumoto, Kazuhiro ; Sato, Norihiro ; Matsumoto, Kunio ; Nakamura, Toshikazu ; Narumi, Ko ; Nukiwa, Toshihiro ; Tanaka, Masao. / Gene transduction of NK4, HGF antagonist, inhibits in vitro invasion and in vivo growth of human pancreatic cancer. In: Clinical and Experimental Metastasis. 2002 ; Vol. 19, No. 5. pp. 417-426.
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AU - Matsumoto, Kunio

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