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首页> 外文期刊>Cancer research: The official organ of the American Association for Cancer Research, Inc >Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis.
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Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis.

机译：表皮生长因子受体的表达可在人胶质母细胞瘤中鉴定出功能和分子上不同的肿瘤起始细胞，这是神经胶质瘤发生所必需的。

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摘要

Epidermal growth factor receptor (EGFR) is a known diagnostic and, although controversial, prognostic marker of human glioblastoma multiforme (GBM). However, its functional role and biological significance in GBM remain elusive. Here, we show that multiple GBM cell subpopulations could be purified from the specimens of patients with GBM and from cancer stem cell (CSC) lines based on the expression of EGFR and of other putative CSC markers. All these subpopulations are molecularly and functionally distinct, are tumorigenic, and need to express EGFR to promote experimental tumorigenesis. Among them, EGFR-expressing tumor-initiating cells (TIC) display the most malignant functional and molecular phenotype. Accordingly, modulation of EGFR expression by gain-of-function and loss-of-function strategies in GBM CSC lines enhances and reduces their tumorigenic ability, respectively, suggesting that EGFR plays a fundamental role in gliomagenesis. These findings open up the possibility of new therapeutically relevant scenarios, as the presence of functionally heterogeneous EGFR(pos) and EGFR(neg) TIC subpopulations within the same tumor might affect clinical response to treatment.
机译：表皮生长因子受体（EGFR）是已知的人类胶质母细胞瘤（GBM）的诊断且是有争议的预后标志物。但是，其在GBM中的功能作用和生物学意义仍然不清楚。在这里，我们表明，基于EGFR和其他假定的CSC标记物的表达，可以从GBM患者的标本和癌症干细胞（CSC）系中纯化出多个GBM细胞亚群。所有这些亚群在分子和功能上均不同，具有致瘤性，并且需要表达EGFR以促进实验性肿瘤发生。其中，表达EGFR的肿瘤起始细胞（TIC）显示出最恶性的功能和分子表型。因此，通过GBM CSC系中的功能获得和功能丧失策略对EGFR表达的调节分别增强和降低了它们的致瘤能力，这表明EGFR在神经胶质瘤的发生中起着基本作用。这些发现打开了新的治疗相关方案的可能性，因为同一肿瘤内功能异质性EGFR（pos）和EGFR（neg）TIC亚群的存在可能影响对治疗的临床反应。

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