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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References
Pastan I, Gottesman M: Multiple-drug resistance in human cancer. N Engl J Med 316: 1388–1393, 1987
Endicott JA, Ling V: The biochemistry of P-glycoprotein mediated multidrug resistance. Ann Rev Biochem 58: 137–171, 1989
Bigotte L, Arvidson B, Olsson Y: Cytofluorescence localization of adriamycin in the nervous system. Acta Neuropathol 57: 121–129, 1982
Cordon-Cardo C, O'Brien JP, Casals D, Rittman-Grauer L, Biedler JL, Melamed MR, Bertino JR: Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci 86: 695–698, 1989
Meyers MB, Rittmann-Grauer L, O'Brien JP, Safa AR: Characterization of monoclonal antibodies recognizing a Mr 180,000 P-glycoprotein: Differential expression of the Mr 180,000 and Mr 170,000 P-glycoproteins in multidrug-resistant human tumor cells. Cancer Res 49: 3209–3214, 1989
Miyagami M, Smith BH, McKeever PE, Chronwall BM, Greenwood MA, Kornblith PL: Immunocytochemical localization of factor VIII-related antigen in tumors of the central nervous system. J Neuro-Oncol 4: 269–285, 1987
Moller M, van Deurs B, Westergaard E: Vascular permeability to proteins and peptides in the mouse pineal gland. Cell Tiss Res 195: 1–15, 1978
Inaba M, Kabayashi H, Sakurai Y, Johnson RK: Active efflux of daunorubicin and adriamycin in sensitive and resistant sublines of P388 leukemia. Cancer Res 39: 2200–2203, 1979
Chen C, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB: Internal duplication and homology with bacterial transport proteins in the mdrl (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47: 381–389, 1986
Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou J, Drumm ML, Innazi MC, Collins FS, Tsui L: Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 245: 1066–1073, 1989
Goldstein LJ, Galski H, Fojo A, Willingham M, Lai SL, Gazdar A, Pirker R, Green A, Crist W, Brodeur GM, Lieber M, Cossman J, Gottesman MM, Pastan I: Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 81: 116–124, 1989
Fuen L, Landy H, Lu K, Li DJ, Kuo MT, Lampidis T, Green B, Savaraj N: mdrl gene expression in primary malignant brain tumors (Abstract). Proc Ann Meet Am Soc Clin Oncol 8: A343, 1989
Nabors MW, Griffin CA, Zehnbauer BA, Hruban RH, Phillips PC, Grossman SA, Brem H, Colvin OM: Multidrug resistance gene (MDR1) expression in human brain tumors. J Neurosurg 75: 941–946, 1991
Matsumoto T, Tani E, Kaba K, Kochi N, Shindo H, Yamamoto Y, Sakamoto H, Furuyama J: Amplification and expression of a multidrug resistance gene in human glioma cell lines. J Neurosurg 72: 96–101, 1990
Reddy PG, Graham GM, Datta S, Guarini L, Moulton TA, Jiang H, Gottesman MM, Ferrone S, Fisher PB: Effect of recombinant fibroblast interferon and recombinant immune interferon on growth and the antigenic phenotype of multidrug-resistant human glioblastoma multiforme cells. J Natl Cancer Inst 83: 1307–1315, 1991
Pastan I, Gottesman MM, Ueda K, Lovelace E, Rutherford AV, Willingham M: A retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells. Proc Natl Acad Sci 85:4486–4490, 1988
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Henson, J.W., Cordon-Cardo, C. & Posner, J.B. P-glycoprotein expression in brain tumors. J Neuro-Oncol 14, 37–43 (1992). https://doi.org/10.1007/BF00170943
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DOI: https://doi.org/10.1007/BF00170943