Home Neoplasma 2006 Neoplasma Vol.53, p.226-231, 2006

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.53, p.226-231, 2006

Title: Induction of drug resistance in embryonal rhabdomyosarcoma treated with conventional chemotherapy is associated with HLA class I increase.
Author: Prados J, Melguizo C, Fernandez JE, Carrillo E, Marchal JA, Boulaiz H, Martinez A, Rodriguez-Serrano F, Aranega A.

Abstract: Effectiveness of conventional cytotoxic treatment of rhabdomyosarcoma (RMS) may be limited by the development of multidrug resistance (MDR) mediated by mdr1 gene. This gene codes for P-glycoprotein (P-gp) which has been related to a immunoregulatory function. Modulation of HLA expression by P-gp has been described in different types of tumor cells including RMS. However, very little is known about biological implications of the P-gp expression in RMS patients treated with conventional chemotherapy. In order to study the problem, we used embryonal RMS tissue samples from treated patients. Our results indicated that positive RMS samples to mdr1 show higher HLA class I expression than those which were negative to mdr1 PCR, what indicates a significant correlation between the expression of both molecules. In addition, we developed two resistant RMS cell lines (A-204-1 and 2) using similar concentrations of actinomycin D as are plasma levels in clinical situation. Both resistant cell lines showed mdr1 expression and an increase of HLA class I expression which was dose-dependent. These results demonstrated that conventional chemotherapy of embryonal RMS is able to induce resistance which can modulate HLA class I expression and suggest that immunological studies of these tumors may be necessary to the design new specific therapeutic strategies.

Keywords: HLA class I, P-glycoprotein, rhabdomyosarcoma, multidrug resistance, mdr1
Year: 2006, Volume: 53, Issue: Page From: 226, Page To: 231

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