Metabolic Recycling Enhances Proliferation in MYC-Transformed Lymphoma B Cells.
Metabolic Recycling Enhances Proliferation in MYC-Transformed Lymphoma B Cells.
复制标题
DOI：
10.1002/adbi.202200233
复制
发表时间：
2023-02
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
复发对癌症患者的生存有负面影响，这是由于治疗后存活的癌细胞的致瘤能力。需要作出努力，以更好地了解和解决这一问题。这项研究假设放射治疗后的死亡细胞碎片创造了一个有利的微环境，其中含有丰富的代谢物质，促进了剩余的活癌细胞的生长。在这项研究中，活的癌细胞与被紫外线辐射根除的死亡癌细胞共同培养，以模拟治疗后的环境。同位素标记代谢组学被用来研究在放射治疗后环境中生长的癌细胞的代谢行为。研究发现，紫外线根除后的死亡癌细胞是存活癌细胞的“现成”和前体代谢物的营养来源。然后幸存的癌细胞吸收这些代谢物，整合和上调多种重要的代谢过程，从而显著促进体外和可能体内的生长，超越它们固有的快速生长特征。重要的是，这种活跃的代谢物摄取行为只在致癌细胞中观察到，而在非致癌细胞中没有观察到，这为阻断致癌细胞的主动摄取过程而不影响正常细胞的治疗方法提供了机会。在这项研究中，活的癌细胞重新利用治疗后死亡的癌细胞释放的重要代谢物的过程被称为致癌细胞的“代谢循环”。这项研究发现，紫外线治疗后包含死亡癌细胞的环境通过充当活癌细胞可以吸收并并入其新陈代谢的现成和前体代谢物的来源来促进活癌细胞的增殖。这种现象只在致癌细胞中观察到，而在非致癌细胞中没有观察到，这为癌症治疗提供了一个潜在的靶点。
Relapses negatively impact cancer patient survival due to the tumorigenesis ability of surviving cancer cells post-therapy. Efforts are needed to better understand and combat this problem. This study hypothesized that dead cell debris post-radiation therapy creates an advantageous microenvironment rich in metabolic materials promoting the growth of remaining live cancer cells. In this study, live cancer cells are co-cultured with dead cancer cells eradicated by UV radiation to mimic a post-therapy environment. Isotopic labeling metabolomics is used to investigate the metabolic behavior of cancer cells grown in a post-radiation-therapy environment. It is found that post-UV-eradicated dead cancer cells serve as nutritional sources of “off-the-shelf” and precursor metabolites for surviving cancer cells. The surviving cancer cells then take up these metabolites, integrate and upregulate multiple vital metabolic processes, thereby significantly increasing growth in vitro and probably in vivo beyond their intrinsic fast-growing characteristics. Importantly, this active metabolite uptake behavior is only observed in oncogenic but not in non-oncogenic cells, presenting opportunities for therapeutic approaches to interrupt the active uptake process of oncogenic cells without affecting normal cells. The process by which living cancer cells re-use vital metabolites released by dead cancer cells post-therapy is coined in this study as “metabolic recycling” of oncogenic cells. This study finds that a post-ultraviolet-therapy environment containing dead cancer cells promotes the proliferation of live cancer cells by serving as a source of “off-the-shelf” and precursor metabolites which the live cancer cells can absorb and incorporate into their metabolism. This phenomenon is only observed in oncogenic cells, but not in non-oncogenic cells, providing a potential target for cancer therapy.