P-glycoprotein expression in brain tumors.
Overexpression of P-glycoprotein (P-gp) in cancer cells can result in resistance to several chemotherapy agents (multidrug resistance) including doxorubicin and vincristine. The drugs to which resistance develops also penetrate the blood brain barrier poorly. P-gp expression in brain capillary endothelial cells suggests that P-gp may restrict drug entry into brain tumors and thus be another mechanism of drug resistance. To seek evidence for either of these roles in the drug resistance of brain tumors, we examined the location of expression of P-gp in 49 brain tumors, using an anti-P-gp mouse monoclonal antibody and immunohistochemistry. P-gp expression was observed in tumor cells of two glioblastomas and a meningeal sarcoma but not in low-grade primary or metastatic tumors. In low-grade primary tumors, P-gp was present in all vascular endothelial cells. In the vascular endothelial cells of anaplastic primary brain tumors and brain metastases, P-gp expression was heterogeneous or absent. These findings are consistent with a role for P-gp in the resistance of some brain tumors to chemotherapy agents.
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY.
J W
JW
Henson
C
C
Cordon-Cardo
J B
JB
Posner
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000188:drug therapy / Q000556:secondary; D002462:Cell Membrane / Q000737:chemistry; D004351:Drug Resistance; D004730:Endothelium, Vascular / Q000737:chemistry; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins