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.

Favaro, R., Appolloni, I., Pellegatta, S., Sanga, A., Pagella, P., Gambini, E., et al. (2014). Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma. CANCER RESEARCH, 74(6), 1833-1844 [10.1158/0008-5472.CAN-13-1942].

Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma

FAVARO, REBECCA;PELLEGATTA, SERENA;GAMBINI, ELISA;OTTOLENGHI, SERGIO;FOTI, MARIA;NICOLIS, SILVIA KIRSTEN
2014

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.
Articolo in rivista - Articolo scientifico
Animals; Cancer Vaccines; Neoplastic Stem Cells; Immunotherapy; Cell Line, Tumor; Mice; Cell Proliferation; Mice, Transgenic; SOXB1 Transcription Factors; Brain Neoplasms; Peptide Fragments; Tumor Cells, Cultured; Mice, Inbred C57BL; Oligodendroglioma; Transcriptome; Female
English
2014
74
6
1833
1844
none
Favaro, R., Appolloni, I., Pellegatta, S., Sanga, A., Pagella, P., Gambini, E., et al. (2014). Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma. CANCER RESEARCH, 74(6), 1833-1844 [10.1158/0008-5472.CAN-13-1942].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/51495
Citazioni
  • Scopus 77
  • ???jsp.display-item.citation.isi??? 77
Social impact