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Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression.

Behnan, Jinan; Isakson, Paulin; Joel, Mrinal; Cilio, Corrado LU ; Langmoen, Iver A; Vik-Mo, Einar O and Badn, Wiaam LU (2014) In Stem Cells 32(5). p.1110-1123
Abstract
The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These Brain Tumor derived Mesenchymal Stem Cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro, and... (More)
The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These Brain Tumor derived Mesenchymal Stem Cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro, and that the non-MSC population is non-tumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild type GL261 inoculated into GFP-transgenic mice and GL261-GFP cells inoculated into wild type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile, and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients. Stem Cells 2013. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Stem Cells
volume
32
issue
5
pages
1110 - 1123
publisher
AlphaMed Press
external identifiers
  • pmid:24302539
  • wos:000334597200007
  • scopus:84899011003
ISSN
1549-4918
DOI
10.1002/stem.1614
language
English
LU publication?
yes
id
dcdbcf2c-069b-4261-8ef7-1ea05edf6243 (old id 4225271)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24302539?dopt=Abstract
date added to LUP
2014-01-02 22:53:05
date last changed
2017-11-05 03:02:16
@article{dcdbcf2c-069b-4261-8ef7-1ea05edf6243,
  abstract     = {The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These Brain Tumor derived Mesenchymal Stem Cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro, and that the non-MSC population is non-tumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild type GL261 inoculated into GFP-transgenic mice and GL261-GFP cells inoculated into wild type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile, and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients. Stem Cells 2013.},
  author       = {Behnan, Jinan and Isakson, Paulin and Joel, Mrinal and Cilio, Corrado and Langmoen, Iver A and Vik-Mo, Einar O and Badn, Wiaam},
  issn         = {1549-4918},
  language     = {eng},
  number       = {5},
  pages        = {1110--1123},
  publisher    = {AlphaMed Press},
  series       = {Stem Cells},
  title        = {Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression.},
  url          = {http://dx.doi.org/10.1002/stem.1614},
  volume       = {32},
  year         = {2014},
}