Document Detail

Adenovirus-mediated transfection of caspase-8 augments anoikis and inhibits peritoneal dissemination of human gastric carcinoma cells.
MedLine Citation:
PMID:  11585725     Owner:  NLM     Status:  MEDLINE    
Caspase-8 is a member of the cysteine protease family that modulates apoptosis induced by a variety of cell death signals and has recently been found to be activated during the process of anoikis, which is a form of apoptosis caused by loss of anchorage in epithelial cells. We previously demonstrated that the inhibition of anoikis promotes peritoneal dissemination of human gastric carcinoma MKN45 cells, which are anchorage dependent. This suggests that augmentation of anoikis may suppress dissemination of carcinoma cells. To determine whether extrinsic overexpression of caspase-8 can augment anoikis in MKN45 cells, we transfected them with the caspase-8 gene using an adenoviral (Adv) vector (Adv-caspase-8). Here we demonstrate that Adv-caspase-8 infection, at 15 multiplicity of infection (MOI), can augment anoikis in MKN45 cells and suppresses MKN45 peritoneal dissemination in SCID mice. The inhibitory effect on peritoneal dissemination resulted in a prolonged survival compared with that in control mice. In contrast, the Adv-caspase-8 (15 MOI) had no distinct effect on cell viability or growth either of attached MKN45 cells or of s.c. tumor growth in SCID mice. Thus, Adv-mediated overexpression of caspase-8 suppressed peritoneal dissemination mainly through augmentation of anoikis. In addition, Adv-caspase-8-mediated augmentation of anoikis was similarly observed in another gastric carcinoma MKN74 cell line. In contrast, Adv-p53 could not augment anoikis in MKN45 cells. These results imply that Adv-mediated gene transfer of caspase-8 can selectively induce apoptosis in detached carcinoma cells and, thus, shows potential as a novel cancer therapy against dissemination of gastric and probably other carcinoma cells originating from epithelial tissues.
S Nishimura; M Adachi; T Ishida; T Matsunaga; H Uchida; H Hamada; K Imai
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer research     Volume:  61     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-04     Completed Date:  2001-10-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7009-14     Citation Subset:  IM    
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8543, Japan.
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MeSH Terms
Adenocarcinoma / genetics,  pathology,  therapy
Adenoviridae / genetics
Anoikis / physiology*
Caspase 8
Caspase 9
Caspases / biosynthesis,  genetics*,  physiology
Cell Division / physiology
Gene Therapy / methods*
Mice, SCID
Peritoneal Neoplasms / prevention & control*,  secondary
Stomach Neoplasms / genetics,  pathology,  therapy*
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / genetics,  physiology
Xenograft Model Antitumor Assays
Reg. No./Substance:
0/Tumor Suppressor Protein p53; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Casp8 protein, mouse; EC 3.4.22.-/Casp9 protein, mouse; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases

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