Astrocytes enhance the invasion potential of glioblastoma stem-like cells.

Glioblastomas (GBMs) are characterized as highly invasive; the contribution of GBM stem-like cells (GSCs) to the invasive phenotype, however, has not been completely defined. Towards this end, we have defined the invasion potential of CD133+ GSCs and their differentiated CD133- counterparts grown un...

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Main Authors: Barbara H Rath, Joshlean M Fair, Muhammad Jamal, Kevin Camphausen, Philip J Tofilon
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3551925?pdf=render
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author Barbara H Rath
Joshlean M Fair
Muhammad Jamal
Kevin Camphausen
Philip J Tofilon
author_facet Barbara H Rath
Joshlean M Fair
Muhammad Jamal
Kevin Camphausen
Philip J Tofilon
author_sort Barbara H Rath
collection DOAJ
description Glioblastomas (GBMs) are characterized as highly invasive; the contribution of GBM stem-like cells (GSCs) to the invasive phenotype, however, has not been completely defined. Towards this end, we have defined the invasion potential of CD133+ GSCs and their differentiated CD133- counterparts grown under standard in vitro conditions and in co-culture with astrocytes. Using a trans-well assay, astrocytes or astrocyte conditioned media in the bottom chamber significantly increased the invasion of GSCs yet had no effect on CD133- cells. In addition, a monolayer invasion assay showed that the GSCs invaded farther into an astrocyte monolayer than their differentiated progeny. Gene expression profiles were generated from two GSC lines grown in trans-well culture with astrocytes in the bottom chamber or directly in contact with astrocyte monolayers. In each co-culture model, genes whose expression was commonly increased in both GSC lines involved cell movement and included a number of genes that have been previously associated with tumor cell invasion. Similar gene expression modifications were not detected in CD133- cells co-cultured under the same conditions with astrocytes. Finally, evaluation of the secretome of astrocytes grown in monolayer identified a number of chemokines and cytokines associated with tumor cell invasion. These data suggest that astrocytes enhance the invasion of CD133+ GSCs and provide additional support for a critical role of brain microenvironment in the regulation of GBM biology.
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spelling doaj.art-24a034c2741b48c2952d33c251a378a82022-12-21T19:09:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5475210.1371/journal.pone.0054752Astrocytes enhance the invasion potential of glioblastoma stem-like cells.Barbara H RathJoshlean M FairMuhammad JamalKevin CamphausenPhilip J TofilonGlioblastomas (GBMs) are characterized as highly invasive; the contribution of GBM stem-like cells (GSCs) to the invasive phenotype, however, has not been completely defined. Towards this end, we have defined the invasion potential of CD133+ GSCs and their differentiated CD133- counterparts grown under standard in vitro conditions and in co-culture with astrocytes. Using a trans-well assay, astrocytes or astrocyte conditioned media in the bottom chamber significantly increased the invasion of GSCs yet had no effect on CD133- cells. In addition, a monolayer invasion assay showed that the GSCs invaded farther into an astrocyte monolayer than their differentiated progeny. Gene expression profiles were generated from two GSC lines grown in trans-well culture with astrocytes in the bottom chamber or directly in contact with astrocyte monolayers. In each co-culture model, genes whose expression was commonly increased in both GSC lines involved cell movement and included a number of genes that have been previously associated with tumor cell invasion. Similar gene expression modifications were not detected in CD133- cells co-cultured under the same conditions with astrocytes. Finally, evaluation of the secretome of astrocytes grown in monolayer identified a number of chemokines and cytokines associated with tumor cell invasion. These data suggest that astrocytes enhance the invasion of CD133+ GSCs and provide additional support for a critical role of brain microenvironment in the regulation of GBM biology.http://europepmc.org/articles/PMC3551925?pdf=render
spellingShingle Barbara H Rath
Joshlean M Fair
Muhammad Jamal
Kevin Camphausen
Philip J Tofilon
Astrocytes enhance the invasion potential of glioblastoma stem-like cells.
PLoS ONE
title Astrocytes enhance the invasion potential of glioblastoma stem-like cells.
title_full Astrocytes enhance the invasion potential of glioblastoma stem-like cells.
title_fullStr Astrocytes enhance the invasion potential of glioblastoma stem-like cells.
title_full_unstemmed Astrocytes enhance the invasion potential of glioblastoma stem-like cells.
title_short Astrocytes enhance the invasion potential of glioblastoma stem-like cells.
title_sort astrocytes enhance the invasion potential of glioblastoma stem like cells
url http://europepmc.org/articles/PMC3551925?pdf=render
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