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 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.
Ginguené
Carole
C
INSERM U, Université de Lyon, France.
Champier
Jacques
J
Maallem
Said
S
Strazielle
Nathalie
N
Jouvet
Anne
A
Fèvre-Montange
Michelle
M
Ghersi-Egea
Jean-François
JF
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001814:Blood-Testis Barrier / Q000378:metabolism*; D002551:Cerebral Ventricle Neoplasms / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000473:pathology*; D006801:Humans; D007223:Infant; D007797:Laminin / Q000378:metabolism; D055806:Microvessels / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D013120:Spinal Cord Neoplasms / Q000473:pathology*; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism
C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D007797:Laminin; D009363:Neoplasm Proteins; D014841:von Willebrand Factor
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