随着癌细胞增殖并改变其局部环境,与细胞转化相关的遗传改变在很大程度上表达在代谢表型中。并为转移做准备。定性,癌细胞的基本生物化学通常与未转化细胞相同,但是癌细胞会产生局部环境,TME,对基质细胞有敌意,竞争营养。为了扩散,细胞需要充足的营养,要么那些不能由细胞自己制造的,或者必须由更简单的前体制成。然而,在实体瘤中,考虑到快速增殖的潜力,营养供应通常是有限的,和血管质量差。因此,癌细胞可以采用各种策略来获得生存的营养,生长和转移。尽管在标准培养条件下使用已建立的细胞系已经学到了很多东西,从体内代谢研究中可以清楚地看出,这也可能是一种误导,哪种营养素用于能量生产,而不是用于大分子合成的构建模块,甚至在同一个肿瘤内。在这里,我们回顾了代谢网络的运作,以及如何在体内和体外使用稳定的同位素示踪剂揭示TME中营养供应和利用的最新理解。
The genetic alterations associated with cell transformation are in large measure expressed in the metabolic phenotype as cancer cells proliferate and change their local environment, and prepare for metastasis. Qualitatively, the fundamental biochemistry of cancer cells is generally the same as in the untransformed cells, but the cancer cells produce a local environment, the TME, that is hostile to the stromal cells, and compete for nutrients. In order to proliferate, cells need sufficient nutrients, either those that cannot be made by the cells themselves, or must be made from simpler precursors. However, in solid tumors, the nutrient supply is often limiting given the potential for rapid proliferation, and the poor quality of the vasculature. Thus, cancer cells may employ a variety of strategies to obtain nutrients for survival, growth and metastasis. Although much has been learned using established cell lines in standard culture conditions, it is becoming clear from in vivo metabolic studies that this can also be misleading, and which nutrients are used for energy production versus building blocks for synthesis of macromolecules can vary greatly from tumor to tumor, and even within the same tumor. Here we review the operation of metabolic networks, and how recent understanding of nutrient supply in the TME and utilization are being revealed using stable isotope tracers in vivo as well as in vitro.