The MET oncogene is a functional marker of a glioblastoma stem cell subtype

Francesca De Bacco, Elena Casanova, Enzo Medico, Serena Pellegatta, Francesca Orzan, Raffaella Albano, Paolo Luraghi, Gigliola Reato, Antonio D'Ambrosio, Paola Porrati, Monica Patanè, Emanuela Maderna, Bianca Pollo, Paolo M. Comoglio, Gaetano Finocchiaro, Carla Boccaccio

Research output: Contribution to journalArticle

Abstract

The existence of treatment-resistant cancer stem cells contributes to the aggressive phenotype of glioblastoma. However, the molecular alterations that drive stem cell proliferation in these tumors remain unknown. In this study, we found that expression of the MET oncogene was associated with neurospheres expressing the gene signature of mesenchymal and proneural subtypes of glioblastoma. Met expression was almost absent from neurospheres expressing the signature of the classical subtype and was mutually exclusive with amplification and expression of the EGF receptor (EGFR) gene. Met-positive and Met-negative neurospheres displayed distinct growth factor requirements, differentiated along divergent pathways, and generated tumors with distinctive features. The Methigh subpopulation within Met-pos neurospheres displayed clonogenic potential and long-term self-renewal ability in vitro and enhanced growth kinetics in vivo. In Methigh cells, the Met ligand HGF further sustained proliferation, clonogenicity, expression of self-renewal markers, migration, and invasion in vitro. Together, our findings suggest that Met is a functional marker of glioblastoma stem cells and a candidate target for identification and therapy of a subset of glioblastomas.

Original languageEnglish
Pages (from-to)4537-4550
Number of pages14
JournalCancer Research
Volume72
Issue number17
DOIs
Publication statusPublished - Sep 1 2012

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

De Bacco, F., Casanova, E., Medico, E., Pellegatta, S., Orzan, F., Albano, R., Luraghi, P., Reato, G., D'Ambrosio, A., Porrati, P., Patanè, M., Maderna, E., Pollo, B., Comoglio, P. M., Finocchiaro, G., & Boccaccio, C. (2012). The MET oncogene is a functional marker of a glioblastoma stem cell subtype. Cancer Research, 72(17), 4537-4550. https://doi.org/10.1158/0008-5472.CAN-11-3490