Recruited Cells Can Become Transformed and Overtake PDGF-Induced Murine Gliomas <italic>In Vivo</italic> during Tumor Progression
Menée sur un modèle murin de gliome, cette étude montre que des cellules qui ne dérivent pas de la cellule à l'origine d'une tumeur peuvent être recrutées afin d'alimenter la croissance tumorale durant la phase de progression
Background Gliomas are thought to form by clonal expansion from a single cell-of-origin, and progression-associated mutations to occur in its progeny cells. Glioma progression is associated with elevated growth factor signaling and loss of function of tumor suppressors <italic>Ink4a</italic>, <italic>Arf</italic> and <italic>Pten</italic>. Yet, gliomas are cellularly heterogeneous; they recruit and trap normal cells during infiltration.</p> </sec> <sec> <title>Methodology/Principal Findings</title> <p>We performed lineage tracing in a retrovirally mediated, molecularly and histologically accurate mouse model of hPDGFb-driven gliomagenesis. We were able to distinguish cells in the tumor that were derived from the cell-of-origin from those that were not. Phenotypic, tumorigenic and expression analyses were performed on both populations of these cells. Here we show that during progression of hPDGFb-induced murine gliomas, tumor suppressor loss can expand the recruited cell population not derived from the cell-of-origin within glioma microenvironment to dominate regions of the tumor, with essentially no contribution from the progeny of glioma cell-of-origin. Moreover, the recruited cells can give rise to gliomas upon transplantation and passaging, acquire polysomal expression profiles and genetic aberrations typically present in glioma cells rather than normal progenitors, aid progeny cells in glioma initiation upon transplantation, and become independent of PDGFR signaling.</p> </sec> <sec> <title>Conclusions/Significance</title> <p>These results indicate that non-cell-of-origin derived cells within glioma environment in the mouse can be corrupted to become <italic>bona fide</italic> tumor, and deviate from the generally established view of gliomagenesis.</p> </sec>
PLOS ONE 2011