Expression and clinical significance of multidrug resistance proteins in brain tumors.

Abstract

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.

CONCLUSION:

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.

• Authors: Zhenhua Guo, Jin Zhu, Lihua Zhao, Qing Luo, Xianqing Jin
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 29 Pg. 122 (Sep 05 2010) ISSN: 1756-9966 [Electronic] England
• PMID: 20815915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• CAV1 protein, human
• Caveolin 1
• Multidrug Resistance-Associated Proteins
• Vault Ribonucleoprotein Particles
• major vault protein
• GSTP1 protein, human
• Glutathione S-Transferase pi
• DNA Topoisomerases, Type II

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (analysis)
• Blood-Brain Barrier (chemistry)
• Brain Neoplasms (chemistry, drug therapy, pathology)
• Caveolin 1 (analysis)
• Child
• Child, Preschool
• China
• DNA Topoisomerases, Type II (analysis)
• Drug Resistance, Neoplasm
• Endothelial Cells (chemistry)
• Female
• Glutathione S-Transferase pi (analysis)
• Humans
• Immunohistochemistry
• Infant
• Male
• Microscopy, Confocal
• Multidrug Resistance-Associated Proteins (analysis)
• Neoplasm Staging
• Neuroglia (chemistry)
• Vault Ribonucleoprotein Particles (analysis)