Expression of multidrug resistance-associated proteins in paediatric soft tissue sarcomas before and after chemotherapy

  • Authors:
    • Arianna Citti
    • Renata Boldrini
    • Alessandro Inserra
    • Anna Alisi
    • Rosanna Pessolano
    • Angela Mastronuzzi
    • Angelica Zin
    • Luigi De Sio
    • Angelo Rosolen
    • Franco Locatelli
    • Doriana Fruci
  • View Affiliations

  • Published online on: April 10, 2012     https://doi.org/10.3892/ijo.2012.1433
  • Pages: 117-124
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Abstract

Expression of multidrug resistance (MDR) proteins is thought to significantly contribute to the different biological/clinical behaviour of soft tissue sarcomas (STS) of various histological types and clinicopathological stages, as they are responsible for active efflux of cytotoxic drugs from tumour cells. We investigated the expression of 3 MDR proteins, i.e., permeability glycoprotein 1 (P-gp), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance 3 (MDR3), in 43 STS specimens from newly-diagnosed paediatric patients, 31 with rhabdomyosarcoma (RMS) and 12 with non-RMS STS. To assess the influence of chemotherapy on STS drug resistance, the number of MDR-associated protein-positive cells was determined in 15 patients on both primary lesions before chemotherapy and on residual tumour after chemotherapy. At least one of the MDR-associated proteins tested was detected in 84% of primary untreated STS specimens. In these specimens, MRP1 was detected in a high percentage (70%) of the cases, followed by MDR3 in 58% and P-gp in 44%. Many specimens showed co-expression of two different MDR proteins. Interestingly, MDR3 was significantly associated with the presence of PAX3/PAX7-FKHR transcripts in RMS (p<0.05). Moreover, expression of MRP1 and MDR3 was significantly more frequent in group III and IV tumours as compared with those of groups I and II (p<0.01). After chemotherapy MRP1, MDR3 and, to a lesser extent, P-gp expression was found to be increased in most of the samples. The frequent expression of these MDR-associated proteins in primary tumour cells before chemotherapy and the increase of their levels after chemotherapy, suggest that these proteins play a pivotal role in conferring drug resistance and in producing therapy-induced differentiation on STS.

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July 2012
Volume 41 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Citti A, Boldrini R, Inserra A, Alisi A, Pessolano R, Mastronuzzi A, Zin A, De Sio L, Rosolen A, Locatelli F, Locatelli F, et al: Expression of multidrug resistance-associated proteins in paediatric soft tissue sarcomas before and after chemotherapy. Int J Oncol 41: 117-124, 2012
APA
Citti, A., Boldrini, R., Inserra, A., Alisi, A., Pessolano, R., Mastronuzzi, A. ... Fruci, D. (2012). Expression of multidrug resistance-associated proteins in paediatric soft tissue sarcomas before and after chemotherapy. International Journal of Oncology, 41, 117-124. https://doi.org/10.3892/ijo.2012.1433
MLA
Citti, A., Boldrini, R., Inserra, A., Alisi, A., Pessolano, R., Mastronuzzi, A., Zin, A., De Sio, L., Rosolen, A., Locatelli, F., Fruci, D."Expression of multidrug resistance-associated proteins in paediatric soft tissue sarcomas before and after chemotherapy". International Journal of Oncology 41.1 (2012): 117-124.
Chicago
Citti, A., Boldrini, R., Inserra, A., Alisi, A., Pessolano, R., Mastronuzzi, A., Zin, A., De Sio, L., Rosolen, A., Locatelli, F., Fruci, D."Expression of multidrug resistance-associated proteins in paediatric soft tissue sarcomas before and after chemotherapy". International Journal of Oncology 41, no. 1 (2012): 117-124. https://doi.org/10.3892/ijo.2012.1433