超越华堡效应:模拟瘤新陈代谢的动态和上下文依赖性质
Pierre Jacquet1, Angélique Stéphanou1
1Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France.
Cancers
|November 13, 2025
概括
华堡效应在癌症代谢中的作用并不普遍. 瘤细胞代谢动态地适应微环境,受氧和酸度等因素的影响,而不是固定的特征.
科学领域:
- 系统生物学 系统生物学
- 癌症新陈代谢 癌症新陈代谢
- 计算生物学 计算生物学
背景情况:
- 华堡效应是癌症代谢的一个关键特征,越来越多地被认为是取决于背景的.
- 实验证据挑战了对瘤细胞华堡效应的普遍解释.
研究的目的:
- 探索使用混合多尺度模型在压力下瘤中代谢表型的出现.
- 研究细胞代谢和瘤微环境之间的动态相互作用.
主要方法:
- 开发了一种混合多尺度模型,整合了细胞代谢和环境动态.
- 利用基于代理的框架来模拟瘤内的空间和时间异质性.
- 集成的可逆乳酸盐运输和糖溶性流的酸度调节.
主要成果:
- 模拟显示,华堡效应既不是普遍的,也不是静态的.
- 代谢表型基于细胞史和微观环境而动态地出现.
- 这些动态的代谢适应不需要任何遗传改变.
结论:
- 瘤的代谢行为代表了受热力学和酶学因素影响的适应性状态的连续性.
- 瘤中的代谢可塑性是一种系统级的现象.
- 治疗策略可以针对瘤微环境以提高疗效.
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