Role of ABC transporters in the chemoresistance of human gliomas.
Malignant gliomas are frequently chemoresistant and this resistance seems to depend on at least two mechanisms. First, the poor penetration of many anticancer drugs across the blood-brain barrier (BBB), the blood-cerebrospinal fluid barrier (BCSFB) and blood-tumor barrier (BTB), due to their interaction with several ATP-binding cassette (ABC) drug efflux transporters that are overexpressed by the endothelial or epithelial cells of these barriers. Second, resistance may involve the tumor cells themselves. Although ABC drug efflux transporters in tumor cells confer multidrug resistance (MDR) on several other solid tumors, their role in gliomas is unclear. This review focuses on astrocytes and summarizes the current state of knowledge about the expression, distribution and function of ABC transporters in normal and tumor astroglial cells. The recognition of anticancer drugs by ABC transporters in astroglial cells and their participation in the multidrug resistance phenotype of human gliomas is discussed.
Declèves
Xavier
X
INSERM U705 UMR CNRS 7157, Laboratory of Neuropsychopharmacology, Faculty of Pharmacy, Paris, France. xavier.decleves@univ-paris5.fr
Amiel
Alexandra
A
Delattre
Jean-Yves
JY
Scherrmann
Jean-Michel
JM
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D006801:Humans
D018528:ATP-Binding Cassette Transporters