Hafner, Michael and Zawatzky, Rainer and Hirtreiter, Christian and Buurman, Wim A. and Echtenacher, Bernd and Hehlgans, Thomas and Maennel, Daniela N. (2001) Antimetastatic effect of CpG DNA mediated by type IIFN. CANCER RESEARCH, 61 (14). pp. 5523-5528. ISSN 0008-5472
Full text not available from this repository. (Request a copy)Abstract
The mechanisms involved in the antimetastatic effect of CpG-containing DNA were investigated in a mouse model of experimental metastasis, Tumor cell colony formation in lungs or livers of mice after i.v. inoculation with syngeneic fibrosarcoma or thymoma cells was determined. The i.v. injection of plasmid DNA or synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs before tumor cell application strongly inhibited metastasis, Because synthetic CpG-ODN was not directly tumor cytotoxic, the target cells for this CpG-ODN effect were determined. The cytotoxic activity on standard natural killer (NK) targets as well as on fibrosarcoma cells of splenic NK cells and NKT cell-containing liver mononuclear cells derived from CpG-ODN-treated mice was strongly enhanced. Participation of NK/NKT cells in the CpG-induced antimetastatic effect was demonstrated by reduction of the antimetastatic effect in mice depleted of NK/NKT cells and beta (2)-microglobulin-deficient mice. Neutralization of interleukin 12, interleukin 18, or IFN-gamma did not interfere with the CpG-induced antimetastatic effect. However, in sera of CpG-ODN-treated mice, high levels of IFN-alpha were detected, and in IFN-alpha/beta receptor-deficient mice, the CpG-ODN-induced antimetastatic effect was strongly reduced. These data indicate that CpG-ODNs activate NK/NKT cells for antimetastatic activity indirectly via IFN-alpha/beta receptor activation. The exploitation of the stimulatory activity of CpG-ODN for the innate immune system might be a useful strategy for antimetastatic therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MYCOBACTERIUM-BOVIS BCG; NATURAL-KILLER-CELLS; NECROSIS-FACTOR-ALPHA; CDNA-ENCODING PROTEINS; IFN-GAMMA PRODUCTION; BACTERIAL-DNA; SYNTHETIC OLIGONUCLEOTIDES; IMMUNOSTIMULATORY DNA; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Dec 2021 07:03 |
| Last Modified: | 21 Dec 2021 07:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/41258 |
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