Expression and clinical significance of multidrug resistance proteins in brain tumors.
BACKGROUND
To investigate the mechanisms of multidrug resistance of brain tumors, to identify the site of cellular expression of P-gp in human brains in situ and to morphologically determine whether an association may exist between P-gp and caveolin-1.


METHODS
Immunohistochemistry was used to detect the expression and location of P-glycoprotein (P-gp), multidrug resistance-associated protein (MDR), lung resistance-related protein (LRP), topoisomerase II (Topo II) and glutathione-S-π (GST-π) in 30 patient tumor tissues and 5 normal brain tissues. The sections were subjected to double labeling for P-gp (TRITC labeled) and caveolin-1 (FITC labeled). The location and characteristics of expression of the two proteins in the blood brain barrier(BBB) was observed using a laser scanning microscope.


RESULTS
High expression of P-gp was detected in vessel walls and the tissue surrounding the vessels. However, expression of P-gp was low in tumor cells. The expression of the other 4 multidrug resistance proteins was not observed in the vessel walls. Laser scanning microscopy showed P-gp and caveolin-1 co-expression: the two proteins co-localized either in the luminal endothelial compartment or at the border of the luminal/abluminal compartments.


CONCLUSIONS
Chemotherapeutics drugs are interrupted in the end-feet of neuroepithelial cells of the BBB by P-gp, which weakens the chemotherapeutic effect. P-gp marks the BBB, and the transporter is localized in the luminal endothelial compartment where it co-localizes with caveolin-1.
Guo
Zhenhua
Z
Department of Oncology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Zhu
Jin
J
Zhao
Lihua
L
Luo
Qing
Q
Jin
Xianqing
X
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D001812:Blood-Brain Barrier / Q000737:chemistry; D001932:Brain Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D051242:Caveolin 1 / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D002681:China; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000737:chemistry; D005260:Female; D051549:Glutathione S-Transferase pi / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D018613:Microscopy, Confocal; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis; D009367:Neoplasm Staging; D009457:Neuroglia / Q000737:chemistry; D020394:Vault Ribonucleoprotein Particles / Q000032:analysis; D000099187:Major Vault Protein
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051242:Caveolin 1; D004250:DNA Topoisomerases, Type II; D051549:Glutathione S-Transferase pi; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C513055:ABCB1 protein, human; C495540:CAV1 protein, human; C496556:GSTP1 protein, human
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