PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells.
Cell-cell interactions between tumor cells and constituents of their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM) cells and endothelial cells (ECs) establish a purported cancer stem cell niche. We hypothesized t...
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doaj-4bc889b331cf44b09ca81cd65b5195be2020-11-25T01:35:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10739710.1371/journal.pone.0107397PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells.Michael D BrooksErin JacksonNicole M WarringtonJingqin LuoJason T ForysSara TaylorDiane D MaoJeffrey R LeonardAlbert H KimDavid Piwnica-WormsRobi D MitraJoshua B RubinCell-cell interactions between tumor cells and constituents of their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM) cells and endothelial cells (ECs) establish a purported cancer stem cell niche. We hypothesized that genes regulated by these interactions would be important, particularly as therapeutic targets. Using a computational approach, we deconvoluted expression data from a mixed physical co-culture of GBM cells and ECs and identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to direct contact with ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation in vitro and increased tumor growth and aggressiveness in an in vivo intracranial GBM model. Collectively these studies illustrate a novel approach for studying cell-cell interactions and identifying new therapeutic targets like PDE7B in GBM.http://europepmc.org/articles/PMC4159344?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michael D Brooks Erin Jackson Nicole M Warrington Jingqin Luo Jason T Forys Sara Taylor Diane D Mao Jeffrey R Leonard Albert H Kim David Piwnica-Worms Robi D Mitra Joshua B Rubin |
spellingShingle |
Michael D Brooks Erin Jackson Nicole M Warrington Jingqin Luo Jason T Forys Sara Taylor Diane D Mao Jeffrey R Leonard Albert H Kim David Piwnica-Worms Robi D Mitra Joshua B Rubin PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells. PLoS ONE |
author_facet |
Michael D Brooks Erin Jackson Nicole M Warrington Jingqin Luo Jason T Forys Sara Taylor Diane D Mao Jeffrey R Leonard Albert H Kim David Piwnica-Worms Robi D Mitra Joshua B Rubin |
author_sort |
Michael D Brooks |
title |
PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells. |
title_short |
PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells. |
title_full |
PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells. |
title_fullStr |
PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells. |
title_full_unstemmed |
PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells. |
title_sort |
pde7b is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Cell-cell interactions between tumor cells and constituents of their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM) cells and endothelial cells (ECs) establish a purported cancer stem cell niche. We hypothesized that genes regulated by these interactions would be important, particularly as therapeutic targets. Using a computational approach, we deconvoluted expression data from a mixed physical co-culture of GBM cells and ECs and identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to direct contact with ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation in vitro and increased tumor growth and aggressiveness in an in vivo intracranial GBM model. Collectively these studies illustrate a novel approach for studying cell-cell interactions and identifying new therapeutic targets like PDE7B in GBM. |
url |
http://europepmc.org/articles/PMC4159344?pdf=render |
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