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vector-mediated MS-selective transgene expression was markedly impaired in tumor-bearing mice whose MS had already been replaced by infiltrating cancer cells.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.
Fujiwara
Hitoshi
H
Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. hfuji@koto.kpu-m.ac.jp
Kubota
Takeshi
T
Amaike
Hisashi
H
Inada
Satoshi
S
Takashima
Kazuhiro
K
Atsuji
Kiyoto
K
Yoshimura
Mamoru
M
Maemondo
Makoto
M
Narumi
Ko
K
Nukiwa
Toshihiro
T
Matsumoto
Kunio
K
Nakamura
Toshikazu
T
Hagiwara
Akeo
A
Yamagishi
Hisakazu
H
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