RRC ID 3814
Author Tanaka F, Tominaga K, Shiota M, Ochi M, Kuwamura H, Tanigawa T, Watanabe T, Fujiwara Y, Oshitani N, Higuchi K, Iwao H, Arakawa T.
Title Interleukin-10 gene transfer to peritoneal mesothelial cells suppresses peritoneal dissemination of gastric cancer cells due to a persistently high concentration in the peritoneal cavity.
Journal Cancer Gene Ther.
Abstract Interleukin (IL)-10 has potent biological properties including an inhibitory action on the proliferation and metastasis of various cancer cells. However, it is difficult to maintain a high concentration of this cytokine as it has a short half life. In this study, we evaluated whether peritoneal mesothelial cells (PMCs) could be suitable for maintaining a high concentration of IL-10 using adenoviral gene transfer. We also evaluated the therapeutic effects of an intraperitoneal injection with adenoviral vector containing mouse IL-10 gene (Ad-mIL-10) using a mouse peritoneal dissemination model of MKN45 gastric cancer cells. We demonstrated that in vitro transfection efficiency of a recombinant adenovirus containing the bacterial beta-galactosidase gene (Ad-LacZ) was approximately 10-fold higher for primarily isolated PMCs than MKN45. The entire peritoneum was transfected until 3 weeks after an intraperitoneal Ad-LacZ injection. Ad-mIL-10 treatment increased intraperitoneal IL-10 levels until 3 weeks after treatment, and then significantly inhibited peritoneal cancer growth by inhibiting angiogenesis. This treatment also improved cachexia and prolonged mice survival. We thus concluded that IL-10 gene transfer in PMCs could be a new strategy for the prevention of peritoneal dissemination of gastric cancer due to the resulting persistently high IL-10 concentration in the peritoneal cavity.
Volume 15(1)
Pages 51-9
Published 2008-1
DOI 10.1038/sj.cgt.7701104
PII 7701104
PMID 17992202
MeSH Adenoviridae* Animals Cachexia / genetics Cachexia / metabolism Cachexia / therapy Epithelium / metabolism Humans Interleukin-10 / biosynthesis* Interleukin-10 / genetics Lac Operon / genetics Male Mice Mice, Inbred BALB C Mice, Nude Neoplasms, Experimental / genetics Neoplasms, Experimental / metabolism Neoplasms, Experimental / therapy Peritoneal Cavity Peritoneal Neoplasms / genetics Peritoneal Neoplasms / metabolism Peritoneal Neoplasms / secondary Peritoneal Neoplasms / therapy* Rats Rats, Wistar Stomach Neoplasms / genetics Stomach Neoplasms / metabolism Stomach Neoplasms / therapy* Time Factors Transduction, Genetic* Transfection
IF 4.044
Times Cited 15
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY ONCOLOGY GENETICS & HEREDITY
Resource
DNA material AxCAmIL10 (RDB1410)