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Neoplasma Vol.50, p.91-96, 2003
|Title: Modulation of HLA class I expresion in multidrug-resistant human rhabdomyosarcoma cells|
|Author: C., MELGUIZO ; J., PRADOS ; J.A., MARCHAL ; C., VELEZ ; E., CARRILLO ; H., BOULAIZ ; I., SANCHEZ-MONTESINOS ; R., MADEDDU ; A., ARANEGA ;|
|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.
|Keywords: MDR, P-glycoprotein, rhabdomyossarcoma, HLA, verapamil.|
|Year: 2003, Volume: 50, Issue:||Page From: 91, Page To: 96|