Tumor progression and oncogene addiction in a PDGF-B-induced model of gliomagenesis

Filippo Calzolari, Irene Appolloni, Evelina Tutucci, Sara Caviglia, Marta Terrile, Giorgio Corte, Paolo Malatesta

Research output: Contribution to journalArticlepeer-review

Abstract

Platelet-derived growth factor B (PDGF-B) overexpression induces gliomas of different grades from murine embryonic neural progenitors. For the first time, we formally demonstrated that PDGF-B-induced neoplasms undergo progression from nontumorigenic low-grade tumors toward highly malignant forms. This result, showing that PDGF-B signaling alone is insufficient to confer malignancy to cells, entails the requirement for further molecular lesions in this process. Our results indicate that one of these lesions is represented by the down-regulation of the oncosuppressor Btg2. By in vivo transplantation assays, we further demonstrate that fully progressed tumors are PDGF-B-addicted because their tumor-propagating ability is lost when the PDGF-B transgene is silenced, whereas it is promptly reacquired after its reactivation. We provide evidence that this oncogene addiction is not caused by the need for PDGF-B as a mitogen but, rather, to the fact that PDGF-B is required to overcome cell-cell contact inhibition and to confer in vivo infiltrating potential on tumor cells.

Original languageEnglish
Pages (from-to)1373-1382
Number of pages10
JournalNeoplasia (United States)
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 2008

ASJC Scopus subject areas

  • Cancer Research

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