%0 Journal Article
%T Expression and clinical significance of multidrug resistance proteins in brain tumors
%A Zhenhua Guo
%A Jin Zhu
%A Lihua Zhao
%A Qing Luo
%A Xianqing Jin
%J Journal of Experimental & Clinical Cancer Research
%D 2010
%I BioMed Central
%R 10.1186/1756-9966-29-122
%X 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-¦Ð (GST-¦Ð) 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.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.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.Currently, primary malignant brain tumors and brain metastases are still difficult to treat with cytotoxic agents. Even though new chemotherapeutic schedules have improved results of cancer treatment in other parts of the body (e.g., small-cell lung cancer, breast cancer, various leukemias), the efficacy of these new schedules in brain tumors remains poor [1]. In addition to the blood brain barrier(BBB), resistance mechanisms at the tumor cell level may include the intrinsic chemo-insensitivity of brain tumors. The BBB is a major impediment to the entry of many therapeutic drugs into the brain, and over the last decade, it has become clear that multispecific, xenobiotic transporters play a significant role at the BBB [2]. The major de
%U http://www.jeccr.com/content/29/1/122