Journal article
Recruited Cells Can Become Transformed and Overtake PDGF-Induced Murine Gliomas In Vivo during Tumor Progression
PloS one, v 6(7), pp e20605-e20605
06 Jul 2011
PMID: 21754979
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Recruited Cells Can Become Transformed and Overtake PDGF-Induced Murine Gliomas In Vivo during Tumor Progression
- Creators
- Elena I. Fomchenko - Memorial Sloan Kettering Cancer CenterJoseph D. Dougherty - Rockefeller UniversityKarim Y. Helmy - Memorial Sloan Kettering Cancer CenterAmanda M. Katz - Memorial Sloan Kettering Cancer CenterAlexander Pietras - Memorial Sloan Kettering Cancer CenterCameron Brennan - Memorial Sloan Kettering Cancer CenterJason T. Huse - Memorial Sloan Kettering Cancer CenterAna Milosevic - Rockefeller UniversityEric C. Holland - Memorial Sloan Kettering Cancer Center
- Publication Details
- PloS one, v 6(7), pp e20605-e20605
- Publisher
- Public Library Science
- Number of pages
- 14
- Grant note
- Tegger Foundation U54 CA126518; U54 CA143798 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Starr Foundation Swedish Research Council
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurology
- Web of Science ID
- WOS:000292632000003
- Scopus ID
- 2-s2.0-79959921981
- Other Identifier
- 991022004960104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology