Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy.
Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy.
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人类脑脊液调节促进胶质母细胞瘤生长的途径。
DOI：
10.3389/fonc.2021.624145
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发表时间：
2021
影响因子：
4.7
通讯作者：
Guerrero-Cázares H
中科院分区：
文献类型：
--
作者：
Carrano A;Zarco N;Phillipps J;Lara-Velazquez M;Suarez-Meade P;Norton ES;Chaichana KL;Quiñones-Hinojosa A;Asmann YW;Guerrero-Cázares H
胶质母细胞瘤（GBM）是成人中枢神经系统最常见和最具破坏性的原发性癌症。高级别胶质瘤能够改变和响应脑微环境。当GBM肿瘤浸润脑室下区（SVZ）时，它们具有比SVZ远端肿瘤更具侵袭性的临床表现。我们认为，脑脊液（CSF）的接触有助于提高这些肿瘤的GBM恶性特征。我们评估了人CSF对GBM的影响，对暴露于CSF的人原代GBM细胞进行转录组分析，以测量基因表达谱的变化及其对疾病结局的临床相关性。此外，我们评估了CSF暴露的GBM细胞在体外和体内的增殖和迁移的变化。CSF在促进细胞恶性的途径中诱导转录组学变化，如凋亡、存活、细胞运动、血管生成、炎症和葡萄糖代谢。使用TCGA数据库，从响应于CSF的鉴定的转录变化中提取的基因签名被证明是GBM患者存活的预测。此外，CSF在体外诱导GBM细胞的活力、增殖率和自我更新能力以及迁移能力的增加。在体内，与对照相比，GBM细胞与人CSF共注射产生更大和更具增殖性的肿瘤。总之，这些结果提供了直接证据，CSF是通过激活恶性表型特征的复杂基因表达模式来确定肿瘤生长和侵袭的关键因素。这些发现对GBM患者具有诊断和治疗意义。CSF接触引起的变化可能在SVZ近端GBM恶性程度增加中起作用。
Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation than SVZ-distal tumors. We suggest that cerebrospinal fluid (CSF) contact contributes to enhance GBM malignant characteristics in these tumors. We evaluated the impact of human CSF on GBM, performing a transcriptome analysis on human primary GBM cells exposed to CSF to measure changes in gene expression profile and their clinical relevance on disease outcome. In addition we evaluated the proliferation and migration changes of CSF-exposed GBM cells in vitro and in vivo. CSF induced transcriptomic changes in pathways promoting cell malignancy, such as apoptosis, survival, cell motility, angiogenesis, inflammation, and glucose metabolism. A genetic signature extracted from the identified transcriptional changes in response to CSF proved to be predictive of GBM patient survival using the TCGA database. Furthermore, CSF induced an increase in viability, proliferation rate, and self-renewing capacity, as well as the migratory capabilities of GBM cells in vitro. In vivo, GBM cells co-injected with human CSF generated larger and more proliferative tumors compared to controls. Taken together, these results provide direct evidence that CSF is a key player in determining tumor growth and invasion through the activation of complex gene expression patterns characteristic of a malignant phenotype. These findings have diagnostic and therapeutic implications for GBM patients. The changes induced by CSF contact might play a role in the increased malignancy of SVZ-proximal GBM.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
3
作者：
Chaichana KL;Guerrero-Cazares H;Capilla-Gonzalez V;Zamora-Berridi G;Achanta P;Gonzalez-Perez O;Jallo GI;Garcia-Verdugo JM;Quiñones-Hinojosa A
通讯作者：
Quiñones-Hinojosa A
影响因子：
4.8
作者：
Kordula, T;Rydel, RE;Travis, J
通讯作者：
Travis, J
DOI：
10.1016/j.radonc.2015.07.032
发表时间：
2015-08
期刊：
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
影响因子：
--
作者：
Chen L;Chaichana KL;Kleinberg L;Ye X;Quinones-Hinojosa A;Redmond K
通讯作者：
Redmond K
影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A