The distribution of drug-efflux pumps, P-gp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours

Autor: Dirk Sleijfer, Willem Vaalburg, NH Hendrikse, Harry J.M. Groen, Joost Bart, E. G. E. de Vries, Harry Hollema, T Wegman, W.T.A. van der Graaf
Přispěvatelé: Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Targeted Gynaecologic Oncology (TARGON), Clinical pharmacology and pharmacy
Jazyk: angličtina
Rok vydání: 2004
Předmět:
Male
Cancer Research
medicine.medical_specialty
CLINICAL-RELEVANCE
Testicle
P-glycoprotein
testicular tumour
breast cancer resistance-related protein
PROGNOSTIC-FACTORS
Testicular Neoplasms
Internal medicine
medicine
Humans
ATP Binding Cassette Transporter
Subfamily B
Member 1
NON-HODGKINS-LYMPHOMA
MULTIDRUG-RESISTANCE
Blood–testis barrier
ACUTE LYMPHOBLASTIC-LEUKEMIA
biology
blood-testis barrier
Seminoma
GERM-CELL TUMORS
medicine.disease
Sertoli cell
Immunohistochemistry
ENDOTHELIAL-CELLS
medicine.anatomical_structure
Endocrinology
Oncology
Testicular Lymphoma
Cancer research
biology.protein
multidrug resistance-associated protein
ATP-Binding Cassette Transporters
BRAIN-BARRIER
Germ cell tumors
Multidrug Resistance-Associated Proteins
MONOCLONAL-ANTIBODIES
STEM-CELLS
Germ cell
germ cell tumour
Zdroj: European Journal of Cancer, 40(14), 2064-2070. ELSEVIER SCI LTD
Bart, J, Hollema, H, Groen, H J M, De Vries, E G E, Hendrikse, N H, Sleijfer, D T, Wegman, T D, Vaalburg, W & Van Der Graaf, W T A 2004, ' The distribution of drug-efflux pumps, P-gp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours ', European Journal of Cancer, vol. 40, no. 14, pp. 2064-2070 . https://doi.org/10.1016/j.ejca.2004.05.010
European Journal of Cancer, 40(14), 2064-2070. Pergamon
ISSN: 0959-8049
DOI: 10.1016/j.ejca.2004.05.010
Popis: The drug-efflux pumps P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are present in the blood-testis barrier (BTB) and may hamper the delivery of cytotoxic drugs to the testis. The precise localisation of P-gp and MRP1 in testicular tissue and the presence of the efflux pumps MRP2 and breast cancer resistance protein (BCRP) in the BTB are unknown. We therefore studied the localisation of these pumps in the BTB in normal testis (n=12), in non-seminoma (n=10) seminoma (n=10), and testicular lymphoma (n=9). Slides were scored semi-quantitatively for P-gp, MRP1, MRP2 and BCRP and blood vessels with factor VIII antibody. In normal testis, P-gp and BCRP were strongly expressed by myoid cells and luminal capillary endothelial wall and P-gp also by Leydig cells. MRP1 was observed at the basal side of Sertoli cells and on Leydig cells. MRP2 was only weakly expressed by myoid cells. Seminomas and non-seminomas expressed P-gp and/or BCRP and/or MRP1, lymphomas strongly expressed P-gp, weakly expressed BCRP and did not or showed weak expression of MRP1. There was very little staining for MRP2 in the tumours. Newly formed vessels in all tumours only expressed P-gp and BCRP. P-gp, BCRP and MRP1 are present in different cell layers of the normal testis, suggesting the optimal protection of spermatogenesis. In germ cell tumours, this expression pattern may explain the chemoresistance observed to P-gp, BCRP and MRP1 substrates. In germ cell tumours and testicular lymphomas, P-gp and BCRP expression by tumour cells and by newly formed vessels may also contribute to chemoresistance. These findings underscore the importance of removing the affected testis in cases of primary germ cell tumours and testicular lymphomas, irrespective of whether the patient has already undergone chemotherapy. (C) 2004 Elsevier Ltd. All rights reserved.
Databáze: OpenAIRE
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