Cell Reports (Aug 2023)
Coexisting cancer stem cells with heterogeneous gene amplifications, transcriptional profiles, and malignancy are isolated from single glioblastomas
- Francesca De Bacco,
- Francesca Orzan,
- Giovanni Crisafulli,
- Marta Prelli,
- Claudio Isella,
- Elena Casanova,
- Raffaella Albano,
- Gigliola Reato,
- Jessica Erriquez,
- Antonio D’Ambrosio,
- Mara Panero,
- Carmine Dall’Aglio,
- Laura Casorzo,
- Manuela Cominelli,
- Francesca Pagani,
- Antonio Melcarne,
- Pietro Zeppa,
- Roberto Altieri,
- Isabella Morra,
- Paola Cassoni,
- Diego Garbossa,
- Anna Cassisa,
- Alice Bartolini,
- Serena Pellegatta,
- Paolo M. Comoglio,
- Gaetano Finocchiaro,
- Pietro L. Poliani,
- Carla Boccaccio
Affiliations
- Francesca De Bacco
- Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy; Department of Oncology, University of Turin, 10060 Candiolo, Italy
- Francesca Orzan
- Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Giovanni Crisafulli
- IFOM ETS - The AIRC Institute of Molecular Oncology, 20139 Milan, Italy
- Marta Prelli
- Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy; Department of Oncology, University of Turin, 10060 Candiolo, Italy
- Claudio Isella
- Department of Oncology, University of Turin, 10060 Candiolo, Italy; Laboratory of Oncogenomics, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Elena Casanova
- Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Raffaella Albano
- Core Facilities, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Gigliola Reato
- Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy; Department of Oncology, University of Turin, 10060 Candiolo, Italy
- Jessica Erriquez
- Core Facilities, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Antonio D’Ambrosio
- Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Mara Panero
- Unit of Pathology, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Carmine Dall’Aglio
- Unit of Pathology, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Laura Casorzo
- Unit of Pathology, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Manuela Cominelli
- Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
- Francesca Pagani
- Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
- Antonio Melcarne
- Neurosurgery Unit, Città della Salute e della Scienza University Hospital, 10126 Turin, Italy
- Pietro Zeppa
- Neurosurgery Unit, Città della Salute e della Scienza University Hospital, 10126 Turin, Italy; Department of Neurosciences, University of Turin, 10126 Turin, Italy
- Roberto Altieri
- Department of Neurosciences, University of Turin, 10126 Turin, Italy
- Isabella Morra
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
- Paola Cassoni
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
- Diego Garbossa
- Neurosurgery Unit, Città della Salute e della Scienza University Hospital, 10126 Turin, Italy; Department of Neurosciences, University of Turin, 10126 Turin, Italy
- Anna Cassisa
- Laboratory of Oncogenomics, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Alice Bartolini
- Core Facilities, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Serena Pellegatta
- Unit of Immunotherapy of Brain Tumors, Fondazione IRCCS Istituto Neurologico C. Besta, 20133 Milan, Italy
- Paolo M. Comoglio
- IFOM ETS - The AIRC Institute of Molecular Oncology, 20139 Milan, Italy
- Gaetano Finocchiaro
- Department of Neurology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
- Pietro L. Poliani
- Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
- Carla Boccaccio
- Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy; Department of Oncology, University of Turin, 10060 Candiolo, Italy; Corresponding author
- Journal volume & issue
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Vol. 42,
no. 8
p. 112816
Abstract
Summary: Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to tumor subclonal properties is debated. In this study, we describe the systematic derivation, propagation, and characterization of multiple distinct GSCs from single, treatment-naive GBMs (GSC families). The tumorigenic potential of each GSC better correlates with its transcriptional profile than its genetic make-up, with classical GSCs being inherently more aggressive and mesenchymal more dependent on exogenous growth factors across multiple GBMs. These GSCs can segregate and recapitulate different histopathological aspects of the same GBM, as shown in a paradigmatic tumor with two histopathologically distinct components, including a conventional GBM and a more aggressive primitive neuronal component. This study provides a resource for investigating how GSCs with distinct genetic and/or phenotypic features contribute to individual GBM heterogeneity and malignant escalation.
