Department of Stem Cell Biology & Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, PA 19107, USA.
Antioxid Redox Signal. 2012 Jun 1;16(11):1264-84. doi: 10.1089/ars.2011.4243. Epub 2011 Nov 17.
Here, we review certain recent advances in oxidative stress and tumor metabolism, which are related to understanding the contributions of the microenvironment in promoting tumor growth and metastasis. In the early 1920s, Otto Warburg, a Nobel Laureate, formulated a hypothesis to explain the "fundamental basis" of cancer, based on his observations that tumors displayed a metabolic shift toward glycolysis. In 1963, Christian de Duve, another Nobel Laureate, first coined the phrase auto-phagy, derived from the Greek words "auto" and "phagy," meaning "self" and "eating."
Now, we see that these two ideas (autophagy and aerobic glycolysis) physically converge in the tumor stroma. First, cancer cells secrete hydrogen peroxide. Then, as a consequence, oxidative stress in cancer-associated fibroblasts drives autophagy, mitophagy, and aerobic glycolysis.
This "parasitic" metabolic coupling converts the stroma into a "factory" for the local production of recycled and high-energy nutrients (such as L-lactate)-to fuel oxidative mitochondrial metabolism in cancer cells. We believe that Warburg and de Duve would be pleased with this new two-compartment model for understanding tumor metabolism. It adds a novel stromal twist to two very well-established cancer paradigms: aerobic glycolysis and autophagy.
Undoubtedly, these new metabolic models will foster the development of novel biomarkers, and corresponding therapies, to achieve the goal of personalized cancer medicine. Given the central role that oxidative stress plays in this process, new powerful antioxidants should be developed in the fight against cancer.
在这里，我们回顾了氧化应激和肿瘤代谢方面的某些最新进展，这些进展与理解微环境在促进肿瘤生长和转移方面的贡献有关。20 世纪 20 年代初，诺贝尔奖得主奥托·瓦尔堡（Otto Warburg）基于他观察到的肿瘤代谢向糖酵解转变的现象，提出了一个假说，用以解释“癌症的基本基础”。1963 年，另一位诺贝尔奖得主克里斯蒂安·德·迪夫（Christian de Duve）首次创造了自噬一词，该词源自希腊语“auto”和“phagy”，意为“自我”和“吞噬”。
现在，我们看到这两个想法（自噬和有氧糖酵解）在肿瘤基质中物理上融合在一起。首先，癌细胞会分泌过氧化氢。然后，作为后果，癌症相关成纤维细胞中的氧化应激会导致自噬、线粒体自噬和有氧糖酵解。
这种“寄生”代谢偶联将基质转化为局部生产回收和高能营养物质（如 L-乳酸）的“工厂”，为癌细胞的氧化线粒体代谢提供燃料。我们相信，瓦尔堡和德迪夫会对这个理解肿瘤代谢的新双室模型感到满意。它为两个非常成熟的癌症范例（有氧糖酵解和自噬）增添了新的基质扭曲。
毫无疑问，这些新的代谢模型将促进新型生物标志物的开发以及相应疗法的发展，以实现个性化癌症医学的目标。鉴于氧化应激在这个过程中起着核心作用，应该开发新的强大抗氧化剂来对抗癌症。
