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. 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. © 2010 guo et al.