D'Alessandro Giuseppina, Monaco Lucia, Catacuzzeno Luigi, Antonangeli Fabrizio, Santoro Antonio, Esposito Vincenzo, Franciolini Fabio, Wulff Heike, Limatola Cristina
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy.
IRCCS Neuromed, Via Atinense, 86077 Pozzilli, Italy.
Cancers (Basel). 2019 Feb 26;11(3):279. doi: 10.3390/cancers11030279.
Glioblastoma (GBM) is a deadly brain tumor, with fast recurrence even after surgical intervention, radio- and chemotherapies. One of the reasons for relapse is the early invasion of surrounding brain parenchyma by GBM, rendering tumor eradication difficult. Recent studies demonstrate that, in addition to eliminate possible residual tumoral cells after surgery, radiation stimulates the infiltrative behavior of GBM cells. The intermediate conductance of Ca-activated potassium channels (KCa3.1) play an important role in regulating the migration of GBM. Here, we show that high dose radiation of patient-derived GBM cells increases their invasion, and induces the transcription of key genes related to these functions, including the pair. In addition, we demonstrate that radiation increases the expression of KCa3.1 channels, and that their pharmacological inhibition counteracts the pro-invasive phenotype induced by radiation in tumor cells. Our data describe a possible approach to treat tumor resistance that follows radiation therapy in GBM patients.
胶质母细胞瘤（GBM）是一种致命的脑肿瘤，即使在手术干预、放疗和化疗后也会迅速复发。复发的原因之一是GBM早期侵袭周围脑实质，使得肿瘤难以根除。最近的研究表明，除了清除手术后可能残留的肿瘤细胞外，放疗还会刺激GBM细胞的浸润行为。钙激活钾通道（KCa3.1）的中间电导在调节GBM的迁移中起重要作用。在此，我们表明，对患者来源的GBM细胞进行高剂量放疗会增加其侵袭性，并诱导与这些功能相关的关键基因转录，包括该对基因。此外，我们证明放疗会增加KCa3.1通道的表达，并且其药理学抑制可抵消放疗在肿瘤细胞中诱导的促侵袭表型。我们的数据描述了一种可能的方法来治疗GBM患者放疗后出现的肿瘤耐药性。
