Sox2 Is Required to Maintain Cancer Stem Cells in a Mouse Model of High-Grade Oligodendroglioma

被引：83

作者：

Favaro, Rebecca ^{[1
]}

Appolloni, Irene ^{[5
]}

Pellegatta, Serena ^{[2
,3
]}

Sanga, Alexandra Badiola ^{[1
]}

Pagella, Pierfrancesco ^{[1
]}

Gambini, Eleonora ^{[5
]}

Pisati, Federica ^{[4
]}

Ottolenghi, Sergio ^{[1
]}

Foti, Maria ^{[1
]}

Finocchiaro, Gaetano ^{[2
]}

Malatesta, Paolo ^{[5
]}

Nicolis, Silvia K. ^{[1
]}

机构：

[1] Univ Milano Bicocca, Dept Biosci & Biotechnol, I-20126 Milan, Italy

[2] Fdn IRCCS Ist Neurol C Besta, Dept Mol Neurooncol, Milan, Italy

[3] IFOM IEO Campus, European Inst Oncol, Dept Expt Oncol, Milan, Italy

[4] IFOM IEO Campus, FIRC Inst Mol Oncol Fdn IFOM, Tissue Proc Unit, Milan, Italy

[5] IRCCS Azienda Osped Univ San Martino, IST Ist Nazl Ric Canc, Genoa, Italy

来源：

CANCER RESEARCH | 2014年 / 74卷 / 06期

关键词：

TUMOR-INITIATING CELLS; GROWTH-FACTOR; SELF-RENEWAL; PDGF; MEDULLOBLASTOMA; TUMORIGENICITY; PROLIFERATION; NEURONS; SHH; IDENTIFICATION;

D O I：

10.1158/0008-5472.CAN-13-1942

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2014 AACR.

引用

页码：1833 / 1844

页数：12

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