Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.

<h4>Background</h4>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...

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Autores principales:	Elena I Fomchenko, Joseph D Dougherty, Karim Y Helmy, Amanda M Katz, Alexander Pietras, Cameron Brennan, Jason T Huse, Ana Milosevic, Eric C Holland
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/95d7ded787264c348290c92103d44730
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spelling	oai:doaj.org-article:95d7ded787264c348290c92103d447302021-11-18T06:50:43ZRecruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.1932-620310.1371/journal.pone.0020605https://doaj.org/article/95d7ded787264c348290c92103d447302011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21754979/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Elena I FomchenkoJoseph D DoughertyKarim Y HelmyAmanda M KatzAlexander PietrasCameron BrennanJason T HuseAna MilosevicEric C HollandPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e20605 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elena I Fomchenko Joseph D Dougherty Karim Y Helmy Amanda M Katz Alexander Pietras Cameron Brennan Jason T Huse Ana Milosevic Eric C Holland Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
format	article
author	Elena I Fomchenko Joseph D Dougherty Karim Y Helmy Amanda M Katz Alexander Pietras Cameron Brennan Jason T Huse Ana Milosevic Eric C Holland
author_facet	Elena I Fomchenko Joseph D Dougherty Karim Y Helmy Amanda M Katz Alexander Pietras Cameron Brennan Jason T Huse Ana Milosevic Eric C Holland
author_sort	Elena I Fomchenko
title	Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
title_short	Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
title_full	Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
title_fullStr	Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
title_full_unstemmed	Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
title_sort	recruited cells can become transformed and overtake pdgf-induced murine gliomas in vivo during tumor progression.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/95d7ded787264c348290c92103d44730
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Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.

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