Suppression of peritoneal implantation of gastric cancer cells by adenovirus vector-mediated NK4 expression.
Peritoneal dissemination is the most common mode of metastasis in gastric cancer. We previously reported the importance of milky spots (MS), peritoneal lymphoid tissues, as selective sites of cancer implantation in peritoneal dissemination. In the present study, we first demonstrated that intraperitoneal injection of adenovirus vector encoding the GFP gene into tumor-free nude mice resulted in GFP expression at omental and mesenteric MS; MS macrophages were target cells for adenovirus infection. We confirmed that intraperitoneal injection of adenovirus vector encoding the NK4 gene (AdNK4) resulted in NK4 production localized to the peritoneal cavity, especially the omentum. Adenovirus vector-mediated MS-selective transgene expression was markedly impaired in tumor-bearing mice whose MS had already been replaced by infiltrating cancer cells. However, prior injection of AdNK4 successfully inhibited MS-selective cancer cell implantation, resulting in suppression of peritoneal dissemination and prolongation of survival. Adenovirus vector-mediated MS-selective delivery of a therapeutic gene may prevent peritoneal dissemination of gastric cancer.
Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. hfuji@koto.kpu-m.ac.jp
Hitoshi
H
Fujiwara
Takeshi
T
Kubota
Hisashi
H
Amaike
Satoshi
S
Inada
Kazuhiro
K
Takashima
Kiyoto
K
Atsuji
Mamoru
M
Yoshimura
Makoto
M
Maemondo
Ko
K
Narumi
Toshihiro
T
Nukiwa
Kunio
K
Matsumoto
Toshikazu
T
Nakamura
Akeo
A
Hagiwara
Hisakazu
H
Yamagishi
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002465:Cell Movement; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008934:Mitogens / Q000235:genetics / Q000627:therapeutic use*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D019076:Transgenes / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000637:transplantation
C066855:HGF protein, human; D008934:Mitogens; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor