P-glycoprotein expression in brain tumors |
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Authors: | John W Henson Carlos Cordon-Cardo Jerome B Posner |
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Institution: | (1) Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA;(2) Department of Pathology Cancer Center, New York, NY, USA;(3) Present address: Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Boston, MA, USA;(4) Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 10021 New York, NY, USA |
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Abstract: | Summary 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. |
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Keywords: | P-glycoprotein multidrug resistance brain tumor immunohistochemistry |
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