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.
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.
Tanaka
F
F
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Tominaga
K
K
Shiota
M
M
Ochi
M
M
Kuwamura
H
H
Tanigawa
T
T
Watanabe
T
T
Fujiwara
Y
Y
Oshitani
N
N
Higuchi
K
K
Iwao
H
H
Arakawa
T
T
D000256:Adenoviridae; D000818:Animals; D002100:Cachexia / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D007763:Lac Operon / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D010529:Peritoneal Cavity; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection
D016753:Interleukin-10