NATURE:颠覆!肿瘤中疯狂消耗葡萄糖的不是癌细胞

2021-04-10 haibei MedSci原创

值得注意的是,在一系列癌症模型中,髓细胞摄取肿瘤环境中葡萄糖的能力最强,其次是T细胞和癌细胞。相比之下,癌细胞对谷氨酰胺的摄取能力最高。

以往的研究通常表明,肿瘤在氧气存在的情况下消耗大量葡萄糖并产生乳酸盐。癌细胞的特点是通过Warburg代谢消耗葡萄糖,这一过程构成了正电子发射断层扫描(PET)肿瘤成像的基础。但是有氧糖酵解在快速增殖的细胞也被广泛观察到,包括肿瘤浸润的免疫细胞也依赖于葡萄糖,以支持生物合成需求。体内碳标记研究已经证实,葡萄糖可以支持转化细胞和T细胞的合成代谢。此外,谷氨酰胺代谢可以提供替代燃料,并抑制巨噬细胞和T细胞的葡萄糖依赖性分化以及细胞功能。

肿瘤微环境(TME)中免疫细胞代谢受损有助于肿瘤细胞的免疫逃避。然而,在TME中,是否存在由细胞内在程序,或与癌细胞竞争有限的营养物质导致的免疫细胞的代谢失调仍然不清楚。

最近,研究人员使用PET示踪剂来测量特定细胞亚群在TME中的葡萄糖和谷氨酰胺的利用和摄取。值得注意的是,在一系列癌症模型中,髓细胞摄取肿瘤环境中葡萄糖的能力最强,其次是T细胞和癌细胞。相比之下,癌细胞对谷氨酰胺的摄取能力最高。

葡萄糖优先被免疫细胞消耗,而不是癌细胞。

这种独特的营养分区是通过mTORC1信号,以及葡萄糖和谷氨酰胺代谢相关基因的表达以细胞内在方式编程的。抑制谷氨酰胺的摄取增强了整个肿瘤驻留细胞类型的葡萄糖摄取,表明谷氨酰胺代谢抑制葡萄糖摄取,而葡萄糖不是TME中的限制因素。

因此,细胞内在程序分别驱动免疫细胞和癌细胞优先获取葡萄糖和谷氨酰胺。这些营养物质的细胞选择性分区可以被利用来开发肿瘤疗法和成像策略,以增强或监测TME中特定细胞群的代谢程序和活动。

 

原始出处:

Bradley I. Reinfeld et al. Cell-programmed nutrient partitioning in the tumour microenvironment. NATURE (2021). 

 

 

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    2021-06-28 liye789132251
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    2021-04-24 ms6000001814663719

    学习了,

    0

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    2021-04-15 科研科研科研

    免疫细胞和癌细胞优先获取葡萄糖和谷氨酰胺。

    0

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    2021-04-12 ms5000000183725715

    哇哦

    0

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    2021-04-12 yxch36
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    2021-04-11 ms7000000108845907

    厉害了

    0

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    2021-04-10 JZ Yang

    学习了

    0

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