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

Author

Listed:
  • 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
    Yale School of Medicine)

  • Luca Tiberi

    (University of Trento)

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.

Suggested Citation

  • Francesco Antonica & Lucia Santomaso & Davide Pernici & Linda Petrucci & Giuseppe Aiello & Alessandro Cutarelli & Luciano Conti & Alessandro Romanel & Evelina Miele & Toma Tebaldi & Luca Tiberi, 2022. "A slow-cycling/quiescent cells subpopulation is involved in glioma invasiveness," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32448-0
    DOI: 10.1038/s41467-022-32448-0
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