1. Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma
- Author
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Gaetano Finocchiaro, Federica Pisati, Irene Appolloni, Sergio Ottolenghi, Serena Pellegatta, Eleonora Gambini, Alexandra Badiola Sanga, Pierfrancesco Pagella, Silvia K. Nicolis, Paolo Malatesta, Maria Foti, Rebecca Favaro, Favaro, R, Appolloni, I, Pellegatta, S, Sanga, A, Pagella, P, Gambini, E, Pisati, F, Ottolenghi, S, Foti, M, Finocchiaro, G, Malatesta, P, and Nicolis, S
- Subjects
Cancer Research ,medicine.medical_treatment ,Oligodendroglioma ,Mice, Transgenic ,SOXB1 Transcription Factor ,Tumor initiation ,Biology ,Cancer Vaccines ,Brain Neoplasm ,Mice ,Peptide Fragment ,stomatognathic system ,SOX2 ,Cancer stem cell ,Cell Line, Tumor ,Tumor Cells, Cultured ,medicine ,Animals ,Cell Proliferation ,Animal ,Brain Neoplasms ,SOXB1 Transcription Factors ,fungi ,Immunotherapy ,medicine.disease ,Molecular biology ,Peptide Fragments ,Neural stem cell ,Mice, Inbred C57BL ,Oncology ,Cell culture ,embryonic structures ,Neoplastic Stem Cells ,Cancer research ,Female ,Neoplastic Stem Cell ,sense organs ,biological phenomena, cell phenomena, and immunity ,Stem cell ,Transcriptome ,Cancer Vaccine - 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. Cancer Res; 74(6); 1833–44. ©2014 AACR.
- Published
- 2014