文章：

胶质瘤细胞外代谢组的损伤样特征

An Injury-like Signature of the Extracellular Glioma Metabolome

原文发布日期：30 July 2024

DOI: 10.3390/cancers16152705

类型: Article

开放获取: 是

英文摘要：

Aberrant metabolism is a hallmark of malignancies including gliomas. Intracranial microdialysis enables the longitudinal collection of extracellular metabolites within CNS tissues including gliomas and can be leveraged to evaluate changes in the CNS microenvironment over a period of days. However, delayed metabolic impacts of CNS injury from catheter placement could represent an important covariate for interpreting the pharmacodynamic impacts of candidate therapies. Intracranial microdialysis was performed in patient-derived glioma xenografts of glioma before and 72 h after systemic treatment with either temozolomide (TMZ) or a vehicle. Microdialysate from GBM164, an IDH-mutant glioma patient-derived xenograft, revealed a distinct metabolic signature relative to the brain that recapitulated the metabolic features observed in human glioma microdialysate. Unexpectedly, catheter insertion into the brains of non-tumor-bearing animals triggered metabolic changes that were significantly enriched for the extracellular metabolome of glioma itself. TMZ administration attenuated this resemblance. The human glioma microdialysate was significantly enriched for both the PDX versus brain signature in mice and the induced metabolome of catheter placement within the murine control brain. These data illustrate the feasibility of microdialysis to identify and monitor the extracellular metabolome of diseased versus relatively normal brains while highlighting the similarity between the extracellular metabolome of human gliomas and that of CNS injury.

摘要翻译： 

代谢异常是包括胶质瘤在内的恶性肿瘤的典型特征。颅内微透析技术能够纵向采集中枢神经系统组织（包括胶质瘤）的细胞外代谢物，可用于评估数日内中枢神经系统微环境的变化。然而，导管置入导致的中枢神经系统损伤所产生的延迟性代谢影响，可能成为解释候选疗法药效学作用的重要协变量。本研究在替莫唑胺（TMZ）或对照溶剂全身给药前后72小时，对患者来源的胶质瘤异种移植模型进行了颅内微透析。来自IDH突变型胶质瘤患者来源异种移植模型GBM164的微透析液显示出相对于正常脑组织的独特代谢特征，重现了在人胶质瘤微透析液中观察到的代谢特点。出乎意料的是，导管插入非荷瘤动物脑内引发的代谢变化，与胶质瘤本身的细胞外代谢组存在显著重叠。TMZ给药减弱了这种相似性。人胶质瘤微透析液在小鼠模型中同时显著富集了PDX模型与正常脑组织的差异特征，以及导管置入小鼠对照脑内所诱导的代谢组特征。这些数据证明了微透析技术在识别和监测病变脑组织与相对正常脑组织的细胞外代谢组方面的可行性，同时揭示了人胶质瘤细胞外代谢组与中枢神经系统损伤代谢组之间的相似性。

原文链接：

An Injury-like Signature of the Extracellular Glioma Metabolome