| Glioma progression is associated with elevated growth factor signaling and loss of function for the tumor suppressor genes ink4a, arf, and pten. Gliomas are thought to form by clonal expansion from a single cell of origin, and progression-associated mutations to occur in cells of that population. However, gliomas are cellularly heterogeneous, they recruit and trap normal cells during infiltration. Here we show that during progression of hPDGFb-induced murine gliomas, tumor suppressor loss can expand the recruited cell population within the tumor microenvironment to dominate regions of the tumor, with essentially no contribution of progeny of the cell of origin. Moreover, recruited cells can give rise to gliomas upon transplantation and serial passaging, acquiring polysomal expression profiles and genetic aberrations typically present in glioma cells rather than normal progenitors, and becoming independent of PDGFR signaling. These results call into question the generally established view of gliomagenesis, and underscore the effects of glioma microenvironment on normal cells. |
