Skip Navigation



Brain Advance Access published online on November 14, 2006
Brain, doi:10.1093/brain/awl263
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
130/2/476    most recent
awl263v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Sliwa, M.
Right arrow Articles by Kaminska, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sliwa, M.
Right arrow Articles by Kaminska, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received February 21, 2006
Revised June 29, 2006
Accepted August 14, 2006

Article

The invasion promoting effect of microglia on glioblastoma cells is inhibited by cyclosporin A

Marcin Sliwa 1, Darko Markovic 2, Konrad Gabrusiewicz 1, Michael Synowitz 3, Rainer Glass 2, Malgorzata Zawadzka 1, Aleksandra Wesolowska 1, Helmut Kettenmann 2, and Bozena Kaminska 1 *

1 Laboratory of Transcription Regulation, Department of Cell Biology, Nencki Institute of Experimental Biology, Warsaw, Poland
2 Cellular Neuroscience Group, Max Delbrück Center for Molecular Medicine (MDC), Helios Hospital Berlin, Berlin, Germany
3 Cellular Neuroscience Group, Max Delbrück Center for Molecular Medicine (MDC), Helios Hospital Berlin, Berlin, Germany; Department of Neurosurgery, Helios Hospital Berlin, Berlin, Germany

* To whom correspondence should be addressed.
Bozena Kaminska, E-mail: bozenakk{at}nencki.gov.pl


  Abstract

The invasion of tumour cells into brain tissue is a pathologic hallmark of WHO grades II-IV gliomas and contributes significantly to the failure of current therapeutic treatments. Activated microglial cells are abundant in brain tumours and may support tumour invasiveness. We have previously demonstrated that cyclosporin A (CsA) can affect growth of glioma cells in vitro by inhibiting signalling pathways, which are essential for tumour proliferation and invasiveness. In this work, we demonstrate that migration of EGFP-transfected glioblastoma cells in organotypic brain slices was significantly inhibited by treatment with CsA. On average 77% of untreated cells migrated beyond 500 µm, while only 28-33% cells migrated as far in the brain slices treated with CsA (P < 0.001). This inhibitory effect on glioblastoma invasion was lost when glioblastoma cells were injected into microglia-depleted brain slices. Moreover, CsA significantly inhibits intracranial glioma growth in vivo. We demonstrate that microglia-derived factors increase glioma invasiveness in Matrigel assay in vitro and this is associated with activation of the PI-3K/Akt signalling pathway. The invasion promoting effect of microglia is abolished in the presence of CsA. Furthermore, glioma-derived soluble factors induce morphological transformation of microglia and activate MAPK signalling, although production of pro-inflammatory factors was not observed. Our findings that CsA interferes at clinically relevant concentrations with the tumour-promoting role of microglia and impairs invasive growth of glioma cells in vivo may provide a novel therapeutic strategy against gliomas.

Keywords: cyclosporin A; glioma microenvironment; invasiveness; microglia; signal transduction.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 JCOHome page
M. Rodero, Y. Marie, M. Coudert, E. Blondet, K. Mokhtari, A. Rousseau, W. Raoul, C. Carpentier, F. Sennlaub, P. Deterre, et al.
Polymorphism in the Microglial Cell-Mobilizing CX3CR1 Gene Is Associated With Survival in Patients With Glioblastoma
J. Clin. Oncol., December 20, 2008; 26(36): 5957 - 5964.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.