Single cell-derived spheroids capture the self-renewing subpopulations of metastatic ovarian cancer.

Autor: Velletri T; Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy.; Cogentech Società Benefit Srl, Parco Scientifico e Tecnologico della, Sicilia, 95121, Catania, Italy., Villa CE; Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy.; Human Technopole, Viale Rita Levi-Montalcini 1, 20157, Milan, Italy., Cilli D; Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Barzaghi B; Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Lo Riso P; Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Lupia M; Unit of Gynecological Oncology Research, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Luongo R; Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., López-Tobón A; Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy.; Department of Oncology and Hemato-Oncology, University of Milan, Via Santa Sofia 9, 20122, Milan, Italy., De Simone M; National Institute of Molecular Genetic (INGM), 'Romeo and Enrica Invernizzi', 20122, Milan, Italy., Bonnal RJP; National Institute of Molecular Genetic (INGM), 'Romeo and Enrica Invernizzi', 20122, Milan, Italy., Marelli L; Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Piccolo S; IFOM, the FIRC Institute of Molecular Oncology, 20139, Milan, Italy.; Department of Molecular Medicine (DMM), University of Padua School of Medicine, 35128, Padua, Italy., Colombo N; Division of Gynecologic Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy., Pagani M; National Institute of Molecular Genetic (INGM), 'Romeo and Enrica Invernizzi', 20122, Milan, Italy.; IFOM, the FIRC Institute of Molecular Oncology, 20139, Milan, Italy.; Department of Biosciences, University of Milan, Via Santa Sofia 9, 20122, Milan, Italy., Cavallaro U; Unit of Gynecological Oncology Research, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy., Minucci S; Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy. saverio.minucci@ieo.it.; Department of Biosciences, University of Milan, Via Santa Sofia 9, 20122, Milan, Italy. saverio.minucci@ieo.it., Testa G; Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy. giuseppe.testa@ieo.it.; Department of Oncology and Hemato-Oncology, University of Milan, Via Santa Sofia 9, 20122, Milan, Italy. giuseppe.testa@ieo.it.
Jazyk: angličtina
Zdroj: Cell death and differentiation [Cell Death Differ] 2022 Mar; Vol. 29 (3), pp. 614-626. Date of Electronic Publication: 2021 Nov 29.
DOI: 10.1038/s41418-021-00878-w
Abstrakt: High Grade Serous Ovarian cancer (HGSOC) is a major unmet need in oncology, due to its precocious dissemination and the lack of meaningful human models for the investigation of disease pathogenesis in a patient-specific manner. To overcome this roadblock, we present a new method to isolate and grow single cells directly from patients' metastatic ascites, establishing the conditions for propagating them as 3D cultures that we refer to as single cell-derived metastatic ovarian cancer spheroids (sMOCS). By single cell RNA sequencing (scRNAseq) we define the cellular composition of metastatic ascites and trace its propagation in 2D and 3D culture paradigms, finding that sMOCS retain and amplify key subpopulations from the original patients' samples and recapitulate features of the original metastasis that do not emerge from classical 2D culture, including retention of individual patients' specificities. By enabling the enrichment of uniquely informative cell subpopulations from HGSOC metastasis and the clonal interrogation of their diversity at the functional and molecular level, this method provides a powerful instrument for precision oncology in ovarian cancer.
(© 2021. The Author(s).)
Databáze: MEDLINE
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