Expression of the multidrug-resistance P-glycoprotein (Pgp, MDR-1) by endothelial cells of the neovasculature in central nervous system tumors

Abstract

To elucidate the expression of the MDR1 gene products P-glycoprotein (Pgp) in endothelial cells of newly formed blood microvessels in brain tumors, 30 brain tumors were examined by immunohistochemistry using an anti-Pgp monoclonal antibody, JSB-1. Positive reactions for JSB-1 were detected in endothelial cells in newly formed microvessels in all 16 cases of glioma but not in the 4 meningiomas. Although endothelial cells in newly formed microvessels of all 10 metastatic carcinomas showed positive reactions, negative reactions were seen in those of the primary carcinomas. Compared with reactions of the endothelial cells of normal cerebral capillaries, weak reactions were found in the endothelial cells forming glomeruloid proliferation in newly formed microvessels in the eight glioblastomas and at the border of the surrounding cerebral tissue of the metastatic carcinomas. Since the endothelial cells showing glomeruloid proliferation also had a high proliferative cell nuclear antigen labeling index, the present findings demonstrate a negative relationship between positive reactions for Pgp and the proliferative activities of endothelial cells in cerebral capillaries.

Technetium-99m Sestamibi Single Photon Emission Computed Tomography Findings Correlated With P-glycoprotein Expression, Encoded by the Multidrug Resistance Gene-1 Messenger Ribonucleic Acid, in Intracranial Meningiomas

“…32) Pgp was expressed in the tumor cells but not in the endothelial cells of four cases of meningiomas. 30) Pgp and other types of drug resistance-related gene, such as multidrug resistance-associated protein (MRP) and O 6 -methylguanine-DNA methyltransferase, are highly expressed in meningiomas. 7,10,14,34,36) Our study revealed that Pgp was expressed in 14 of 21 (66.7%) meningiomas, MDR-1 mRNA in eight of 11 (72.7%) meningiomas, and that the RI of 99m Tc-MIBI SPECT was correlated significantly with both Pgp and MDR-1 mRNA expression.…”

“…21,28,31) Hydroxyurea may inhibit the growth of meningioma cell lines through an apoptotic mechanism. 30) Interestingly, in vitro exposure of renal cancer cells to low-dose hydroxyurea causes loss of chromosomal aberration, decrease in the number of MDR-1 gene copies, and increased sensitivity to vinblastine. 13) Our findings indicate that 99m Tc-MIBI SPECT, although not useful to determine the proliferative potential, could predict whether meningiomas, especially recurrent or unresectable meningiomas, overexpress Pgp or MDR-1 mRNA which may be an important factor in the sensitivity or resistance to anticancer drugs.…”

Modulation of Multidrug-Resistance-Associated P-Glycoprotein in Human U-87 MG and HUV-ECC Cells with Antisense Oligodeoxynucleotides to MDR1 mRNA

“…Endothelial cells can have a relatively high P-gp expression already under physiologi-cal conditions, which correspond to its manifold metabolic and protective tasks within the blood-brain barrier [36][37][38][39][40]. In glioblastomas, the newly formed vessels express high amounts of P-gp [41].…”

Drug-Resistance in Central Nervous System Tumors: From the Traditional Cell-Resistance Model to the Genetically Driven Approaches on Therapy

“…Several studies show overexpression of the Pgp in brain tumor samples, as well as in brain-derived cell lines [6,7,8,9,10,11,12,13]. These studies used different methods to evaluate MDR-1 gene expression, such as immunohistochemistry, Western and Northern Blotting and RT-PCR.…”