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

  • Guo Z
  • Zhu J
  • Zhao L
 et al. 
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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.

Author-supplied keywords

  • Blood-Brain Barrier
  • Blood-Brain Barrier: chemistry
  • Brain Neoplasms
  • Brain Neoplasms: chemistry
  • Brain Neoplasms: drug therapy
  • Brain Neoplasms: pathology
  • Caveolin 1
  • Caveolin 1: analysis
  • Child
  • Child, Preschool
  • China
  • DNA Topoisomerases, Type II
  • DNA Topoisomerases, Type II: analysis
  • Drug Resistance, Neoplasm
  • Endothelial Cells
  • Endothelial Cells: chemistry
  • Female
  • Glutathione S-Transferase pi
  • Glutathione S-Transferase pi: analysis
  • Humans
  • Immunohistochemistry
  • Infant
  • Male
  • Microscopy, Confocal
  • Multidrug Resistance-Associated Proteins
  • Multidrug Resistance-Associated Proteins: analysis
  • Neoplasm Staging
  • Neuroglia
  • Neuroglia: chemistry
  • P-Glycoprotein
  • P-Glycoprotein: analysis
  • Vault Ribonucleoprotein Particles
  • Vault Ribonucleoprotein Particles: analysis

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Authors

  • Zhenhua Guo

  • Jin Zhu

  • Lihua Zhao

  • Qing Luo

  • Xianqing Jin

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