肿瘤微环境下的代谢重编程调控

Regulation of metabolic reprogramming in the tumor microenvironment

肿瘤的发生、增殖和转移与其微环境密切相关。肿瘤细胞通常被不同类型的细胞层层包围和设防,这些细胞包括成纤维细胞、免疫细胞及神经纤维和细胞外基质,其对肿瘤细胞设下防线使得肿瘤细胞处于低氧或者营养匮乏状态,迫使肿瘤细胞通过调控自身代谢来从周围环境中摄取充足的营养物质以此抵御免疫细胞的杀伤。本文从两个方面来阐述肿瘤细胞的代谢重编程的调控作用,一方面在营养压力条件下,肿瘤细胞以特殊的方式获取和利用各种营养物质来支持其迅速和无限制的增殖,其中除了传统的营养物质,还包括乳酸、酮体、乙酸、支链氨基酸等非传统的代谢原料,这些物质在肿瘤的发展过程中也起着至关重要的作用;另一方面氧气和营养的匮乏使得肿瘤细胞通过代谢的改变影响和调控周围免疫细胞及成纤维细胞,肿瘤组织的细胞基质成分肿瘤相关成纤维细胞能够提供多种营养物质或生长因子来调控肿瘤细胞的代谢,而肿瘤细胞的多种代谢产物能够影响周围免疫细胞的正常功能,抑制其抗肿瘤作用,最终使得微环境向有利于肿瘤细胞增殖和发展的方向进行转变。

The occurrence,growth and metastasis of tumors are associated with its microenvironment.Cancer cells are surrounded by different kinds of cells,such as cancer-associated fibroblasts,immune cells.These cells establish a defensive microenvironment against tumors under the condition of hypoxia or nutrient deprivation.Under this complicated microenvironment,cancer cells reprogram their metabolic signatures to resist the killing function of immune cells.In this paper,we describe the regulation of metabolic reprogramming of cancer cells in two perspectives.On the one hand,in addition to traditional nutrients,tumor cells can acquire and utilize other nutrients in a special way to support rapid and unrestricted proliferation,such as lactic acid,ketone bodies,acetic acid,and branched-chain amino acids.These substances also play a vital role in the development of tumors.On the other hand,cancer cells can affect and regulate the surrounding immune cells and fibroblasts through metabolic changes under the lack of oxygen and nutrition.Cancer-associated fibroblasts can provide a variety of nutrients or growth factors to regulate the metabolism,meanwhile multiple metabolites from cancer cells inhibit the normal functions and the anti-tumor effects of surrounding immune cells.Ultimately,the microenvironment is transformed to be favorable for proliferation and development of tumors.