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乙酸是人类质母细胞瘤和大脑转移的生物能基质
Tomoyuki Mashimo1, Kumar Pichumani2, Vamsidhara Vemireddy1
1Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Cell
|December 20, 2014
概括
像质母细胞瘤这样的大脑瘤可以通过酸循环利用酸作为能量,而不仅仅是葡萄糖. 这种代谢适应在各种脑瘤中很常见,促进了它们的快速生长.
科学领域:
- 生物化学 生物化学
- 在瘤学瘤学.
- 代谢研究的研究.
背景情况:
- 质母细胞瘤和大脑转移是具有不良预后的侵袭性脑瘤.
- 之前的研究表明,在脑瘤中葡萄糖氧化强烈,但葡萄糖提供的乙-CoA碳素不到50%.
- 推动脑瘤生长的代谢途径仍然不完全理解.
研究的目的:
- 研究用于脑瘤能量代谢的替代碳来源.
- 为了确定大脑瘤是否可以氧化乙酸和/或谷氨酸.
- 为了将乙酸氧化与患者瘤中的特定酶表达相关联.
主要方法:
- 利用 (13)C-NMR光谱法,追踪小鼠正型脑瘤中的代谢途径.
- 使用的标记基质:[1,2-(13) C]乙酸盐,[1,6-(13) C]葡萄糖和[U-(13) C]胺.
- 在人脑瘤患者体内验证的乙酸氧化.
- 评估了乙-CoA合成酶2 (ACSS2) 酶的表达.
主要成果:
- 小鼠的大脑瘤表现出氧化[1,2-(13) C]乙酸盐的能力,同时氧化[1,6-(13) C]葡萄糖.
- 大脑瘤没有氧化[U-(13) C]谷氨.
- 在人脑瘤患者的体内酸盐氧化得到证实并与ACSS2表达相关.
结论:
- 多种不同的大脑瘤具有共同的代谢表型,其特征是通过酸循环通过乙酸氧化.
- 这种乙利用途径是满足恶性脑瘤高能量和生物合成需求的重要适应.
- 向乙酸代谢可能是针对脑癌的新疗法策略.
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