Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression Journal Article
| Authors: | Fomchenko, E. I.; Dougherty, J. D.; Helmy, K. Y.; Katz, A. M.; Pietras, A.; Brennan, C.; Huse, J. T.; Milosevic, A.; Holland, E. C. |
| Article Title: | Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression |
| Abstract: | 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 Ink4a, Arf and Pten. Yet, gliomas are cellularly heterogeneous; they recruit and trap normal cells during infiltration. Methodology/Principal Findings: 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. Conclusions/Significance: These results indicate that non-cell-of-origin derived cells within glioma environment in the mouse can be corrupted to become bona fide tumor, and deviate from the generally established view of gliomagenesis. © 2011 Fomchenko et al. |
| Keywords: | signal transduction; platelet derived growth factor; controlled study; gene mutation; nonhuman; animal cell; mouse; phenotype; animal tissue; gene expression profiling; animal experiment; animal model; in vivo study; cell population; platelet derived growth factor receptor; carcinogenesis; cell lineage; cell type; stem cell; disease model; tumor suppressor gene; cell transformation; glioma cell; glioblastoma; nucleotide sequence; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; murinae; polysome; gene loss; microenvironment; arf protein; cyclin dependent kinase inhibitor 2a; tumor growth; cell transplantation; retrovirus |
| Journal Title: | PLoS ONE |
| Volume: | 6 |
| Issue: | 7 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2011-07-01 |
| Start Page: | e20605 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0020605 |
| PROVIDER: | scopus |
| PMCID: | PMC3130733 |
| PUBMED: | 21754979 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 17 August 2011" - "Art. No.: e20605" - "Source: Scopus" |
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