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Modulation of HLA class I expression in multidrug-resistant human rhabdomyosarcoma cells

Melguizo, Consolacion and Prados Salazar, José Carlos and Marchal Corrales, Juan Antonio and Vélez, Celia and Carrillo Delgado, Esmeralda Esperanza and Boulaiz, Houria and Sánchez Montesinos, I. and Madeddu, Roberto Beniamino and Aránega, A. (2003) Modulation of HLA class I expression in multidrug-resistant human rhabdomyosarcoma cells. Neoplasma, Vol. 50 (2), p. 91-96. ISSN 0028-2685. Article.

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Abstract

An abnormal HLA expression has been detected in some tumors including rhabdomyosarcoma (RMS). Classical cytotoxic treatment of these tumors, the most common childhood soft tissue malignancy, may induce multidrug resistance (MDR) associated with the expression of a 170-kDa membrane-associated glycoprotein (P-glycoprotein). In order to analyse the connection between modulation of HLA expression and the development of the MDR phenotype mediated by P-glycoprotein in RMS, we used three resistant RMS cell lines; two of these resistant cell lines (TE.32.7.DAC and RD-DAC) were established by in vitro exposure to actinomycin D, a drug of choice in the treatment of RMS; the resistant RMS- GR cell line was established from an embryonal RMS tumor after polychemotherapy. Our results showed that all the resistant cell lines showed a significant increase in the expression of HLA class I surface antigens in comparison to drug-sensitive cells. Blockade of P-glycoprotein with verapamil led to a decrease in HLA class I expression in RMS resistant cell lines. However, no modulation of HLA class II expression was observed in any of the three analyzed cell lines. These findings support the hypothesis that the development of resistance mediated by mdr 1/P-glycoprotein, directly influences the expression of HLA class I in RMS cells, inducing to upregulation. This effect may be relevant to the application in RMS of immunotherapy against tumor-associated antigens presented by HLA class I molecules.

Item Type:Article
ID Code:7287
Status:Published
Refereed:Yes
Uncontrolled Keywords:MDR, P-glycoprotein, rhabdomyosarcoma (RMS), HLA, verapamil
Subjects:Area 05 - Scienze biologiche > BIO/17 Istologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Vydavatel'stvo Slovenskej Akademie Vied Veda
ISSN:0028-2685
Deposited On:23 Mar 2012 11:59

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