Cancer Cell Biology
Concomitant increase of LMP1 and CD25 (IL-2-receptor α) expression induced by IL-10 in the EBV-positive NK lines SNK6 and KAI3
Miki Takahara,
Loránd L. Kis,
Noémi Nagy,
Anquan Liu,
Yasuaki Harabuchi,
George Klein,
Eva Klein,
Corresponding Author
Miki Takahara
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Japan
Fax: +46-833-0498.
Microbiology and Tumor Biology Center, Karolinska Institutet, Nobelsväg 16, 17177, Stockholm, SwedenSearch for more papers by this authorLoránd L. Kis
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorNoémi Nagy
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorAnquan Liu
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorYasuaki Harabuchi
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Japan
Search for more papers by this authorGeorge Klein
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorEva Klein
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorMiki Takahara,
Loránd L. Kis,
Noémi Nagy,
Anquan Liu,
Yasuaki Harabuchi,
George Klein,
Eva Klein,
Corresponding Author
Miki Takahara
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Japan
Fax: +46-833-0498.
Microbiology and Tumor Biology Center, Karolinska Institutet, Nobelsväg 16, 17177, Stockholm, SwedenSearch for more papers by this authorLoránd L. Kis
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorNoémi Nagy
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorAnquan Liu
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorYasuaki Harabuchi
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Japan
Search for more papers by this authorGeorge Klein
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorEva Klein
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorAbstract
Extranodal, nasal NK/T-cell lymphomas are regularly Epstein-Barr virus (EBV)-positive, with a type II latency pattern, expressing thus EBNA-1 and LMP1. The contribution of EBV to the tumor development is not known. Similarly to normal natural killer (NK) cells, cell lines derived from malignancies with a NK phenotype require IL-2 for in vitro proliferation. In our effort to explore the contribution of EBV, particularly the role of the LMP1 protein, to the pathogenesis of the NK lymphoma we found that its expression, studied in the NK-lines SNK6 and KAI3, depended on the supply of IL-2 or other cytokines. In the absence of IL-2 other cytokines, such as IL-10 and IFN-γ, could maintain LMP1, but the cells did not proliferate. When grown in IL-2, the SNK6 cells produced IL-10 and IFN-γ, and these cytokines mediated the expression of LMP1. IL-10 treatment enhanced, while IFN-γ receptor blocking antibody reduced, the expression of CD25 and CD54 in the EBV-positive, but not in the EBV-negative lines. IL-10 treated cells required lower amount of IL-2 for proliferation compared to the untreated cells. This effect was seen only with the EBV-positive NK lines in which LMP1 and CD25 were concomitantly upregulated. By this mechanism EBV could have an important role in the development of NK lymphoma since the inflammatory component in the tumor tissue can provide these cytokines. © 2006 Wiley-Liss, Inc.
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