A novel strategy against bone invasion of oral cancer

对抗口腔癌骨侵袭的新策略

• 批准号: 23592957
• 负责人: NOGUCHI Makoto
• 金额: $ 3.24万
• 依托单位: University of Toyama
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592957/
• 关键词: 口腔癌; 顎骨浸潤; 免疫; 破骨細胞分化; 免疫学

Despite CD4+T cells have been demonstrated to play an important role for bone destruction in the microenvironment of inflammatory diseases, very little work has been done to demonstrate the contribution of these cell types to cancer bone invasion. In the present study, we investigated the mechanism of interaction between regulatory T cells (Tregs) and osteoclasts in a murine model of oral cancer to elucidate the role of Tregs in the bone invasion of oral cancer. Tregs were purified from the tumor of mouse oral cancer model and then cocultured with bone marrow cells. Secreted tartrate-resistant acid phosphatase (TRACP) 5b was determined as a marker of osteoclast number. Attenuation of osteoclast-derived TRACP5b was observed in the coculture of tumor derived Tregs and bone marrow cells, and this attenuation of TRACP5b was ameliorated by neutralization of cytotoxic T-lymphocyte-associated antigens-4 (CTLA-4).

尽管 CD4+T 细胞已被证明在炎症性疾病微环境中的骨破坏中发挥重要作用，但很少有工作来证明这些细胞类型对癌症骨侵袭的贡献。在本研究中，我们在口腔癌小鼠模型中研究了调节性T细胞（Tregs）与破骨细胞之间的相互作用机制，以阐明Tregs在口腔癌骨侵袭中的作用。从小鼠口腔癌模型的肿瘤中纯化Treg细胞，然后与骨髓细胞共培养。分泌的抗酒石酸酸性磷酸酶（TRACP）5b被确定为破骨细胞数量的标志物。在肿瘤来源的 Tregs 和骨髓细胞的共培养物中观察到破骨细胞来源的 TRACP5b 的减弱，并且 TRACP5b 的这种减弱可通过中和细胞毒性 T 淋巴细胞相关抗原 4 (CTLA-4) 得到改善。

项目成果

Effect of clinically-relevant concentrations of zoledronate acid on cultured humanoral cancer cells

临床相关浓度的唑来膦酸对培养的人口腔癌细胞的影响

• 发表时间: 2011
• 作者: Inoue S.;Arai N.;Tomihara K.;Noguchi M.
• 通讯作者: Noguchi M.

CTLA4-mediated inhibitory effect on osteoclastgenesis by Tregs in oral cancer

CTLA4介导的Tregs对口腔癌破骨细胞生成的抑制作用

• 发表时间: 2013
• 作者: Tomihara K;Noguchi M
• 通讯作者: Noguchi M

Aging-associated B7-DC+ B cells enhance anti-tumor immunity via Th1 and Th17 induction.

• DOI: 10.1111/j.1474-9726.2011.00764.x
• 发表时间: 2012-02
• 期刊: Aging cell
• 影响因子: 7.8
• 作者: Tomihara K;Shin T;Hurez VJ;Yagita H;Pardoll DM;Zhang B;Curiel TJ;Shin T
• 通讯作者: Shin T

Characterization of regulatory T cells (Tregs) in oral cancer

口腔癌中调节性 T 细胞 (Treg) 的表征

• 发表时间: 2012
• 作者: Tomihara K;Inoue S;Takei R;Imaue S;Arai N;Noguchi M
• 通讯作者: Noguchi M

Characterization of regulatory T cells(Tregs) in oral cancer.

口腔癌中调节性 T 细胞 (Treg) 的表征。

• 发表时间: 2012
• 作者: 冨原 圭;井上さやか;武井理恵;今上修一;新井直也;野口 誠
• 通讯作者: 野口 誠