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A slow-cycling/quiescent cells subpopulation is involved in glioma invasiveness

A slow-cycling/quiescent cells subpopulation is involved in glioma invasiveness

Francesco Antonica , Lucia Santomaso , Davide Pernici , Linda Petrucci , Giuseppe Aiello , Alessandro Cutarelli , Luciano Conti , Alessandro Romanel , Evelina…

Monday, Aug 15

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Francesco Antonica ,

Lucia Santomaso ,

Davide Pernici ,

Linda Petrucci ,

Giuseppe Aiello ,

Alessandro Cutarelli ,

Luciano Conti , Alessandro Romanel , Evelina Miele , Toma Tebaldi & Luca Tiberi Abstract Pediatric and adult high-grade gliomas are the most common primary malignant brain tumors, with poor prognosis due to recurrence and tumor infiltration after therapy. Quiescent cells have been implicated in tumor recurrence and treatment resistance, but their direct visualization and targeting remain challenging, precluding their mechanistic study. Here, we identify a population of malignant cells expressing Prominin-1 in a non-proliferating state in pediatric high-grade glioma patients. Using a genetic tool to visualize and ablate quiescent cells in mouse brain cancer and human cancer organoids, we reveal their localization at both the core and the edge of the tumors, and we demonstrate that quiescent cells are involved in infiltration of brain cancer cells. Finally, we find that Harmine, a DYRK1A/B inhibitor, partially decreases the number of quiescent and infiltrating cancer cells. Our data point to a subpopulation of quiescent cells as partially responsible of tumor invasiveness, one of the major causes of brain cancer morbidity. Introduction Pediatric and adult high-grade gliomas are the most common primary malignant brain tumors, with a median survival of just a few years. Conventional therapies, including surgery, radiotherapy, and pharmacotherapy (typically chemotherapy with temozolomide), have not resulted in major improvements in the survival outcomes of patients with high-grade gliomas 1 . […]

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