P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) Localize in the Microvessels Forming the Blood-Tumor Barrier in Ependymomas
Ependymomas are neuroepithelial tumors that arise from the ependymal layer bordering the cerebral ventricles and spinal canal. Intracranial ependymoma represents a major encephalic tumor in children, while spinal ependymoma develops more frequently in adults. To understand the pharmacoresistance tha...
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Published in | Brain pathology (Zurich, Switzerland) Vol. 20; no. 5; pp. 926 - 935 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.09.2010
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Subjects | |
Online Access | Get full text |
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Summary: | Ependymomas are neuroepithelial tumors that arise from the ependymal layer bordering the cerebral ventricles and spinal canal. Intracranial ependymoma represents a major encephalic tumor in children, while spinal ependymoma develops more frequently in adults. To understand the pharmacoresistance that characterizes this tumoral entity, we analyzed the level of expression and localization of three major efflux transport proteins with a multidrug resistance function, P‐glycoprotein, multidrug resistance‐related protein 1 (MRP1) and breast cancer resistance protein (BCRP), in a series of 25 ependymomas from both children and adults. Real‐time‐PCR analysis showed that all three genes were expressed in all tumors, with no apparent correlation between the level of expression and either age or tumor grade. The MRP1 transcript was expressed at a significantly higher level in spinal tumors than in intracranial tumors. The expression of the proteins corresponding to these genes was confirmed by Western blot analysis. In an immunohistochemical study, P‐glycoprotein and BCRP were shown to be associated with the tumoral vessels, where they presented a luminal localization, a prerequisite for their efflux drug activity into the blood. These data indicate that a biochemical, transporter‐dependent blood–tumor barrier may exist in ependymomas, which may reduce the tumoral bioavailability of lipophilic and amphiphilic anticancer drugs. |
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Bibliography: | istex:9385C248FECCC9F976F9CB15041875ABC4E0C817 ArticleID:BPA389 ark:/67375/WNG-ZRTHHXBN-9 This work was supported by INSERM, Association “Amélie La vie,” and Fondation Planiol. MFM and JFGE contributed equally to the coordination of the work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 1015-6305 1750-3639 |
DOI: | 10.1111/j.1750-3639.2010.00389.x |