COX-2 blockade immunologically suppresses brain metastasis of lung cancer

COX-2阻断免疫学抑制肺癌脑转移

• 批准号: 24700998
• 负责人: FUJITA Mitsugu
• 金额: $ 2.83万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24700998/
• 关键词: 肺がん; 転移性脳腫瘍; 非ステロイド系抗炎症薬; 免疫抑制性細胞; グリオーマ; マイクロ RNA; がん免疫

Associations between the regular use of NSAIDs and reduced cancer risks in human have been shonw. NSAIDs function as COX-2 inhibitors that prevent the production of PGE2, which induces MDSCs in cancer-bearing hosts. We thus hypothesized that COX-2 blockade would suppress brain metastasis of cancers by inhibiting MDSC development and their chemokine-mediated accumulation in the tumor microenvironment (TME). In both mouse and human brain metastasis cases, the expression levels of COX-2 and CCL2, a chemokine primarily attracting MDSCs, were increased in the tumor tissues compared with the periphery or normal brain. Concomitantly, the infiltration of MDSCs was observed at high levels in the tumor tissues. In the mouse brain tumor models using LL/2 murine lung cancer cell line, treatment with NSAIDs inhibited brain metastasis formation with the suppression of MDSCs. Our findings show that the COX-2 pathway promotes brain metastases of lung cancers by development and accumulation of MDSCs.

经常使用非甾体抗炎药和降低人类癌症风险之间的关系已经被证明是正确的。非甾体抗炎药起COX-2抑制剂的作用，可以阻止PGE2的产生，PGE2可以在携带癌症的宿主中诱导MDSCs。因此，我们假设COX-2阻断剂可能通过抑制MDSC的发展及其趋化因子在肿瘤微环境(TME)中的积聚来抑制肿瘤的脑转移。在小鼠和人脑转移病例中，COX-2和CCL2在肿瘤组织中的表达水平均高于周围或正常脑组织。同时，肿瘤组织中可见高水平的MDSCs浸润。在LL/2小鼠肺癌模型中，NSAIDs通过抑制MDSCs抑制脑转移的形成。我们的发现表明，COX-2途径通过MDSCs的发展和积聚促进肺癌的脑转移。

项目成果

Differential activity of interferon-α8 promoter is regulated by Oct-1 and a SNP that dictates prognosis of glioma.

• DOI: 10.4161/onci.19964
• 发表时间: 2012-07-01
• 期刊: Oncoimmunology
• 影响因子: 7.2
• 作者: Kohanbash G;Ishikawa E;Fujita M;Ikeura M;McKaveney K;Zhu J;Sakaki M;Sarkar SN;Okada H
• 通讯作者: Okada H

非小細胞肺癌の転移性脳腫瘍に対する治療戦略- driver oncogeneを標的とした個別化治療への展望

非小细胞肺癌转移性脑肿瘤的治疗策略——针对驱动癌基因的个性化治疗前景

• 发表时间: 2013
• 作者: Okuda T;Kanada Y;Yoshioka H;Tasaki T;Fujita M;Nakagawa K;Kato A
• 通讯作者: Kato A

Prophylactic COX-2 inhibition suppresses brain metastasis of lung cancer by inhibiting myeloid-derived suppressor cells.

预防性 COX-2 抑制通过抑制骨髓源性抑制细胞来抑制肺癌脑转移。

• 发表时间: 2014
• 作者: Fujita M;Miura R;Nakata S;Okuda T;Komohara Y;Kuzushima K;Kato A;Yo hie O.
• 通讯作者: Yo hie O.

Efficacy of preoperative FDG-PET or malignant brain tumor

术前 FDG-PET 或恶性脑肿瘤的疗效

• 发表时间: 2012
• 作者: Tasaki N;Okuda T;Yoshioka H;Takada H;Fujita M;Kato A
• 通讯作者: Kato A

グリオーマ幹細胞テモダール耐性機序におけるABC輸送体の役割

ABC转运蛋白在胶质瘤干细胞Temodar耐药机制中的作用

• 发表时间: 2013
• 作者: Yoshioka H;Fujita M;Okuda T;Tasaki T;Kato A
• 通讯作者: Kato A