| RRC ID |
41631
|
| 著者 |
Tanji H, Yahata H, Hayamizu K, Shinozaki K, Okimoto T, Sakaguchi T, Asahara T.
|
| タイトル |
Augmentation of local antitumor immunity in liver by interleukin-2 gene transfer via portal vein.
|
| ジャーナル |
Cancer Gene Ther
|
| Abstract |
Metastasis to the liver remains an important problem in the treatment of patients with gastrointestinal cancer. We examined the mechanism and effect on liver metastasis of in vivo interleukin-2 (IL-2) gene transfer to the liver. RCN-9 cells derived from F344 rat colon adenocarcinoma were injected into syngeneic rats via the ileocecal vein to induce liver tumors. A total of 2.5x10(9) pfu of adenovirus vector harboring the human IL-2 gene (AdCMVhIL-2), or 2.5x10(9) pfu of control vector encoding beta-galactosidase was administered before RCN-9 cell challenge. On day 14, mean tumor weight was 4.0+/-2.4 g in the control group, whereas IL-2-transduced livers had no tumors. Survival of AdCMVhIL-2-treated rats was significantly longer than that of control rats (P<.01). Flow cytometry demonstrated that the proportion of natural killer (NK) cells had increased among sinusoidal cells collected from IL-2-transduced livers. These cells were highly cytotoxic to RCN-9 cells in vitro in the presence of a physiological high concentration of recombinant IL-2. Preventative effects of IL-2 transduction of the liver against liver metastasis were lost after depletion of NK cells by treatment with anti-asialo GM1 antibodies. Our results indicate that IL-2 gene transfer to the liver prevents liver metastasis by continuously providing physiological high concentrations of IL-2 in the liver, thereby activating sinusoidal NK cells.
|
| 巻・号 |
9(8)
|
| ページ |
655-64
|
| 公開日 |
2002-8-1
|
| DOI |
10.1038/sj.cgt.7700483
|
| PMID |
12136426
|
| MeSH |
Animals
Base Sequence
Colonic Neoplasms / pathology
DNA Primers
Interleukin-2 / genetics*
Interleukin-2 / metabolism
Killer Cells, Natural / immunology
Liver / immunology
Liver / metabolism
Liver Neoplasms, Experimental / immunology*
Liver Neoplasms, Experimental / secondary
Male
Portal Vein*
Rats
Rats, Inbred F344
Transfection*
|
| IF |
4.534
|
| 引用数 |
6
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RCN-9(RCB0511)
YAC-1(RCB1165) |
