title: Suppression of metastasis of human pancreatic cancer to the liver by transportal injection of recombinant adenoviral NK4 in nude mice.
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.
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Murakami
authors.forename: Eishi
authors.initials: E
authors.lastname: Nagai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Michiyo
authors.initials: M
authors.lastname: Saimura
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Naoki
authors.initials: N
authors.lastname: Inadome
authors.forename: Kunio
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Maemondo
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007274:Injections, Intraperitoneal; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008934:Mitogens / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013154:Spleen / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C066855:HGF protein, human; D008934:Mitogens; D017228:Hepatocyte Growth Factor