title: Modulation of dendritic cell function by the radiation-mediated secretory protein γ-synuclein.
abstract: Recently, γ-synuclein (SNCG), which is also known as breast cancer-specific gene-1, has been demonstrated to be an adverse and aggressive marker in breast cancer. In our previous study, SNCG was significantly upregulated in irradiated human breast cancer cells. The aim of this study was to investigate whether radiation-induced, tumor-derived SNCG can influence dendritic cell (DC) function in immune systems. The phenotypical and functional changes of DCs in the presence or absence of SNCG were investigated by FACS analysis, ELISA, and real-time PCR. The ability of SNCG-treated DCs to influence T cells was also examined by coculturing with T cells. The treatment of DCs with SNCG protein inhibited the surface expression of the co-stimulatory molecules CD40 and CD86, and decreased the mRNA levels of pro-inflammatory cytokines. The SNCG-treated DCs inhibited T-cell proliferation slightly, but distinctively increased the population of regulatory T cells. In addition, the production of TGF-β from T cells was significantly increased when they were cocultured with SNCG-treated DCs. Taken together, these results demonstrate that tumor-derived SNCG contributes to immunosuppressive effects via the inhibition of DC differentiation and activation, thus making it a potential target for cancer treatment.
authors.affiliation: Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: S-M
authors.initials: SM
authors.lastname: Kang
authors.affiliation: Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: M-H
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: K-H
authors.initials: KH
authors.lastname: Song
authors.affiliation: Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: S-G
authors.initials: SG
authors.lastname: Hwang
authors.affiliation: Department of Biotechnology, CHA University , Seongnam 463-400, Republic of Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, CHA University , Seongnam 463-400, Republic of Korea.
authors.forename: D-S
authors.initials: DS
authors.lastname: Lim
authors.affiliation: Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences , Seoul 139-706, Republic of Korea.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Song