Intraperitoneal administration of an adenovirus vector carrying REIC/Dkk-3 suppresses peritoneal dissemination of scirrhous gastric carcinoma.
Expression levels of the novel tumor suppressor gene REIC/Dkk-3 are reduced in many human cancers. We have previously showed that an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) induced apoptosis of cancer cells selectively and exerted bystander antitumor effects via ER stress. We examined possible effects of Ad-REIC in a peritoneal dissemination model of scirrhous gastric carcinoma (SGC). Among various types of gastric cancer, SGC continues to be associated with the worst prognosis due to a high incidence of metastases in the peritoneal cavity. We found that a single intraperitoneal injection of Ad-REIC suppressed tumor dissemination and disease progression. Immunomodulation by Ad-REIC led to recruitment of natural killer cells inside tumor nodules. We conclude that Ad-REIC gene therapy may be a potential tool in combinatorial approaches to achieve curative effects in SGC.
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558, Japan.
Swe Swe
SS
Than
Ken
K
Kataoka
Masakiyo
M
Sakaguchi
Hitoshi
H
Murata
Fernando
F
Abarzua
Chika
C
Taketa
Gang
G
Du
Masakazu
M
Yashiro
Kazuyoshi
K
Yanagihara
Yasutomo
Y
Nasu
Hiromi
H
Kumon
Nam-Ho
NH
Huh
D048868:Adaptor Proteins, Signal Transducing; D002293:Adenocarcinoma, Scirrhous / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018925:Chemokines; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*
D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger