RRC ID 42167
著者 Sako A, Kitayama J, Koyama H, Ueno H, Uchida H, Hamada H, Nagawa H.
タイトル Transduction of soluble Flt-1 gene to peritoneal mesothelial cells can effectively suppress peritoneal metastasis of gastric cancer.
ジャーナル Cancer Res
Abstract The prognosis of gastric cancer with peritoneal metastasis has not improved. Despite many promising studies, gene therapy has limited clinical application because of the lack of suitable vector systems to enable selective gene transduction to tumor cells. The aim of this study was to clarify whether gene therapy targeted to peritoneal mesothelial cells (PMCs) can inhibit peritoneal dissemination of gastric cancer. In vitro experiments showed that adenovirus expressing LacZ infected human omental tissue-derived PMCs more efficiently than human gastric cancer cell lines MKN1 and MKN45. When adenovirus expressing LacZ was injected into the peritoneal cavity of nude mice, the expression was detected in the peritoneum for at least 4 weeks. Furthermore, when adenovirus expressing soluble Flt-1 (Ad-sFLT-1) was i.p. administered in vivo, a high level of sFlt-1 protein could be detected in peritoneal lavage for 8 weeks. When MKN45 cells were i.p. inoculated 3 days after adenoviral vector injection, Ad-sFLT-1 markedly reduced the number of metastatic nodules larger than 1 mm in diameter on the peritoneal surface, and significantly prolonged the survival of nude mice without any significant side effects. Thus, peritoneal dissemination was significantly suppressed by a single i.p. injection of Ad-sFlt-1. Anti-angiogenic gene therapy targeted to PMCs could be a novel and practical strategy against peritoneal dissemination of gastric cancer, because it does not require tumor-specific gene transfer.
巻・号 64(10)
ページ 3624-8
公開日 2004-5-15
DOI 10.1158/0008-5472.CAN-04-0304
PII 64/10/3624
PMID 15150121
MeSH Adenoviridae / genetics Animals Cell Line, Tumor Extracellular Matrix Proteins / genetics* Female Genetic Therapy / methods* Humans Lac Operon / genetics Mice Mice, Inbred BALB C Mice, Nude Myosin Heavy Chains Nonmuscle Myosin Type IIB Peritoneal Neoplasms / genetics* Peritoneal Neoplasms / prevention & control* Peritoneal Neoplasms / secondary Peritoneum / cytology Peritoneum / metabolism Peritoneum / physiology Stomach Neoplasms / genetics* Stomach Neoplasms / pathology Stomach Neoplasms / therapy* Transfection Vascular Endothelial Growth Factor Receptor-1 Xenograft Model Antitumor Assays
IF 9.727
引用数 49
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 MKN1(RCB1003) MKN45(RCB1001)