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. 1989 Jan;86(2):695–698. doi: 10.1073/pnas.86.2.695

Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites.

C Cordon-Cardo 1, J P O'Brien 1, D Casals 1, L Rittman-Grauer 1, J L Biedler 1, M R Melamed 1, J R Bertino 1
PMCID: PMC286540  PMID: 2563168

Abstract

Endothelial cells of human capillary blood vessels at the blood-brain and other blood-tissue barrier sites express P-glycoprotein as detected by mouse monoclonal antibodies against the human multidrug-resistance gene product. This pattern of endothelial cell expression may indicate a physiological role for P-glycoprotein in regulating the entry of certain molecules into the central nervous system and other anatomic compartments, such as the testes. These tissues, which limit the access of systemic drugs, are known pharmacologic sanctuaries for metastatic cancer. P-glycoprotein expression in capillary endothelium of brain and testes and not other tissues (i.e., kidney and placenta) may in part explain this phenomenon and could have important implications in cancer chemotherapy.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bech-Hansen N. T., Till J. E., Ling V. Pleiotropic phenotype of colchicine-resistant CHO cells: cross-resistance and collateral sensitivity. J Cell Physiol. 1976 May;88(1):23–31. doi: 10.1002/jcp.1040880104. [DOI] [PubMed] [Google Scholar]
  2. Biedler J. L., Riehm H. Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross-resistance, radioautographic, and cytogenetic studies. Cancer Res. 1970 Apr;30(4):1174–1184. [PubMed] [Google Scholar]
  3. Braverman I. M., Yen A. Ultrastructure of the human dermal microcirculation. II. The capillary loops of the dermal papillae. J Invest Dermatol. 1977 Jan;68(1):44–52. doi: 10.1111/1523-1747.ep12485165. [DOI] [PubMed] [Google Scholar]
  4. Brightman M. W., Klatzo I., Olsson Y., Reese T. S. The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci. 1970 Mar;10(3):215–239. doi: 10.1016/0022-510x(70)90151-6. [DOI] [PubMed] [Google Scholar]
  5. Cordon-Cardo C., Finstad C. L., Bander N. H., Melamed M. R. Immunoanatomic distribution of cytostructural and tissue-associated antigens in the human urinary tract. Am J Pathol. 1987 Feb;126(2):269–284. [PMC free article] [PubMed] [Google Scholar]
  6. Dux E., Joó F. Effects of histamine on brain capillaries. Fine structural and immunohistochemical studies after intracarotid infusion. Exp Brain Res. 1982;47(2):252–258. doi: 10.1007/BF00239384. [DOI] [PubMed] [Google Scholar]
  7. Dym M., Fawcett D. W. The blood-testis barrier in the rat and the physiological compartmentation of the seminiferous epithelium. Biol Reprod. 1970 Dec;3(3):308–326. doi: 10.1093/biolreprod/3.3.308. [DOI] [PubMed] [Google Scholar]
  8. Evans A. E., Gilbert E. S., Zandstra R. The increasing incidence of central nervous system leukemia in children. (Children's Cancer Study Group A). Cancer. 1970 Aug;26(2):404–409. doi: 10.1002/1097-0142(197008)26:2<404::aid-cncr2820260222>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  9. Faustmann P. M., Dermietzel R. Extravasation of polymorphonuclear leukocytes from the cerebral microvasculature. Inflammatory response induced by alpha-bungarotoxin. Cell Tissue Res. 1985;242(2):399–407. doi: 10.1007/BF00214554. [DOI] [PubMed] [Google Scholar]
  10. Fojo A. T., Ueda K., Slamon D. J., Poplack D. G., Gottesman M. M., Pastan I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci U S A. 1987 Jan;84(1):265–269. doi: 10.1073/pnas.84.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hamada H., Tsuruo T. Purification of the 170- to 180-kilodalton membrane glycoprotein associated with multidrug resistance. 170- to 180-kilodalton membrane glycoprotein is an ATPase. J Biol Chem. 1988 Jan 25;263(3):1454–1458. [PubMed] [Google Scholar]
  12. Hasegawa H., Shapiro W. R., Posner J. B. Chemotherapy of experimental metastatic brain tumors in female Wistar rats. Cancer Res. 1979 Jul;39(7 Pt 1):2691–2697. [PubMed] [Google Scholar]
  13. Hsu S. M., Soban E. Color modification of diaminobenzidine (DAB) precipitation by metallic ions and its application for double immunohistochemistry. J Histochem Cytochem. 1982 Oct;30(10):1079–1082. doi: 10.1177/30.10.6182185. [DOI] [PubMed] [Google Scholar]
  14. Jackson D. V., Jr, Sethi V. S., Spurr C. L., McWhorter J. M. Pharmacokinetics of vincristine in the cerebrospinal fluid of humans. Cancer Res. 1981 Apr;41(4):1466–1468. [PubMed] [Google Scholar]
  15. Kartner N., Evernden-Porelle D., Bradley G., Ling V. Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies. 1985 Aug 29-Sep 4Nature. 316(6031):820–823. doi: 10.1038/316820a0. [DOI] [PubMed] [Google Scholar]
  16. Nesbit M. E., Jr, Robison L. L., Ortega J. A., Sather H. N., Donaldson M., Hammond D. Testicular relapse in childhood acute lymphoblastic leukemia: association with pretreatment patient characteristics and treatment. A report for Childrens Cancer Study Group. Cancer. 1980 Apr 15;45(8):2009–2016. doi: 10.1002/1097-0142(19800415)45:8<2009::aid-cncr2820450805>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  17. Parnavelas J. G., Kelly W., Burnstock G. Ultrastructural localization of choline acetyltransferase in vascular endothelial cells in rat brain. Nature. 1985 Aug 22;316(6030):724–725. doi: 10.1038/316724a0. [DOI] [PubMed] [Google Scholar]
  18. Safa A. R., Glover C. J., Meyers M. B., Biedler J. L., Felsted R. L. Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. J Biol Chem. 1986 May 15;261(14):6137–6140. [PubMed] [Google Scholar]
  19. Sugawara I., Kataoka I., Morishita Y., Hamada H., Tsuruo T., Itoyama S., Mori S. Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealed by a monoclonal antibody, MRK 16. Cancer Res. 1988 Apr 1;48(7):1926–1929. [PubMed] [Google Scholar]
  20. Tattersall M. H., Sodergren J. E., Dengupta S. K., Trites D. H., Modest E. J., Frei E., 3rd Pharmacokinetics of actinoymcin D in patients with malignant melanoma. Clin Pharmacol Ther. 1975 Jun;17(6):701–708. doi: 10.1002/cpt1975176701. [DOI] [PubMed] [Google Scholar]
  21. Thiebaut F., Tsuruo T., Hamada H., Gottesman M. M., Pastan I., Willingham M. C. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7735–7738. doi: 10.1073/pnas.84.21.7735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yen A., Braverman I. M. Ultrastructure of the human dermal microcirculation: the horizontal plexus of the papillary dermis. J Invest Dermatol. 1976 Mar;66(3):131–142. doi: 10.1111/1523-1747.ep12481678. [DOI] [PubMed] [Google Scholar]

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