Suppressive control of glioma invasions via inhibition of sodium ion/proton exchanger 1

通过抑制钠离子/质子交换器 1 抑制神经胶质瘤侵袭

• 批准号: 23592130
• 负责人: YANO Hajime
• 金额: $ 3.24万
• 依托单位: Ehime University
• 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-23592130/
• 关键词: 神経膠腫; 潜行性浸潤; ナトリウムイオン/プロトン交換輸送体１; EIPA; TGFbeta シグナル; ナトリウム/プロトン交換輸送体１; 血管新生; TGFbeta; 扁平上皮がん; リンパ節転移; NHE1; グリオーマ; マイクログリア; 脳マクロファージ; 活性酸素; 臨床検体

Preclinical evaluations for the development of a novel anti-tumor invasion medicine by utilization of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) which had exhibited promising potential in vitro were performed, aiming at developing a novel powerful therapy against gliomas of which treatment has long been unimproved. On the way of the explorations of modes of action of EIPA, a characteristic blood vessel was found to contribute to the glioma cell invasions, and an implication that activation process of TGFbeta1 may participate in this step was obtained. Furthermore, the validity to consider EIPA as an anti-tumor invasion medicine was confirmed from the observation of contributions of the target of EIPA sodium ion/proton exchanger1 (NHE1) on lymph node metastasis of head and neck squamous cell carcinoma cells (SCC). Highly metastatic subline-cell of a SCC acquired enhanced expression of NHE1 compared with the non-metastatic parental cell line, and knockdown of NHE1 reduced the metastasis.

利用5-（n -乙基- n -异丙基）-阿米洛利（EIPA）开发一种新型抗肿瘤侵袭药物的临床前评估，旨在开发一种治疗胶质瘤的新型强效药物。在探索EIPA的作用方式的过程中，我们发现了一个特征性的血管参与了胶质瘤细胞的侵袭，并暗示TGFbeta1的激活过程可能参与了这一步骤。此外，通过观察EIPA钠离子/质子交换器1 （NHE1）靶点对头颈部鳞状细胞癌（SCC）淋巴结转移的作用，证实了EIPA作为抗肿瘤侵袭药物的有效性。与非转移的亲代细胞系相比，高转移的SCC亚素细胞获得了NHE1的增强表达，NHE1的下调减少了转移。