title: Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma.
abstract: The stem cell-determining transcription factor Sox2 is required for the maintenance of normal neural stem cells. In this study, we investigated the requirement for Sox2 in neural cancer stem-like cells using a conditional genetic deletion mutant in a mouse model of platelet-derived growth factor-induced malignant oligodendroglioma. Transplanting wild-type oligodendroglioma cells into the brain generated lethal tumors, but mice transplanted with Sox2-deleted cells remained free of tumors. Loss of the tumor-initiating ability of Sox2-deleted cells was reversed by lentiviral-mediated expression of Sox2. In cell culture, Sox2-deleted tumor cells were highly sensitive to differentiation stimuli, displaying impaired proliferation, increased cell death, and aberrant differentiation. Gene expression analysis revealed an early transcriptional response to Sox2 loss. The observed requirement of oligodendroglioma stem cells for Sox2 suggested its relevance as a target for therapy. In support of this possibility, an immunotherapeutic approach based on immunization of mice with SOX2 peptides delayed tumor development and prolonged survival. Taken together, our results showed that Sox2 is essential for tumor initiation by mouse oligodendroglioma cells, and they illustrated a Sox2-directed strategy of immunotherapy to eradicate tumor-initiating cells.
authors.affiliation: Authors' Affiliations: Department of Biotechnology and Biosciences, University of Milano-Bicocca; Department of Molecular Neuro-Oncology, Fondazione I.R.C.C.S. Istituto Neurologico C.Besta; Department of Experimental Oncology, European Institute of Oncology at IFOM-IEO Campus; Tissue Processing Unit, The FIRC Institute of Molecular Oncology Foundation-IFOM, IFOM-IEO Campus, Milano; and IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Favaro
authors.forename: Irene
authors.initials: I
authors.lastname: Appolloni
authors.forename: Serena
authors.initials: S
authors.lastname: Pellegatta
authors.forename: Alexandra Badiola
authors.initials: AB
authors.lastname: Sanga
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Pagella
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gambini
authors.forename: Federica
authors.initials: F
authors.lastname: Pisati
authors.forename: Sergio
authors.initials: S
authors.lastname: Ottolenghi
authors.forename: Maria
authors.initials: M
authors.lastname: Foti
authors.forename: Gaetano
authors.initials: G
authors.lastname: Finocchiaro
authors.forename: Paolo
authors.initials: P
authors.lastname: Malatesta
authors.forename: Silvia K
authors.initials: SK
authors.lastname: Nicolis
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000502:physiology*; D009837:Oligodendroglioma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology; D055748:SOXB1 Transcription Factors / Q000276:immunology / Q000502:physiology*; D059467:Transcriptome; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse