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 Ca2+-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 IL-4/IL-4R 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.

Radiation increases functional KCa3.1 expression and invasiveness in glioblastoma / D'Alessandro, Giuseppina; Monaco, Lucia; Catacuzzeno, Luigi; Antonangeli, Fabrizio; Santoro, Antonio; Esposito, Vincenzo; Franciolini, Fabio; Wulff, Heike; Limatola, Cristina. - In: CANCERS. - ISSN 2072-6694. - 11:3(2019). [10.3390/cancers11030279]

Radiation increases functional KCa3.1 expression and invasiveness in glioblastoma

D'Alessandro, Giuseppina;Monaco, Lucia;Antonangeli, Fabrizio;Santoro, Antonio
Resources
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Esposito, Vincenzo
Resources
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Limatola, Cristina
2019

Abstract

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 Ca2+-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 IL-4/IL-4R 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.
2019
glioblastoma; IL-4; KCa3.1; invasion; radiation
01 Pubblicazione su rivista::01a Articolo in rivista
Radiation increases functional KCa3.1 expression and invasiveness in glioblastoma / D'Alessandro, Giuseppina; Monaco, Lucia; Catacuzzeno, Luigi; Antonangeli, Fabrizio; Santoro, Antonio; Esposito, Vincenzo; Franciolini, Fabio; Wulff, Heike; Limatola, Cristina. - In: CANCERS. - ISSN 2072-6694. - 11:3(2019). [10.3390/cancers11030279]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1270234
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