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 Miele, Toma Tebaldi and Luca Tiberi ()
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Francesco Antonica: University of Trento
Lucia Santomaso: University of Trento
Davide Pernici: University of Trento
Linda Petrucci: University of Trento
Giuseppe Aiello: University of Trento
Alessandro Cutarelli: University of Trento
Luciano Conti: University of Trento
Alessandro Romanel: University of Trento
Evelina Miele: Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS
Toma Tebaldi: University of Trento
Luca Tiberi: University of Trento

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32448-0

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