Detail publikace

Proteomic signature of neuroblastoma cells UKF-NB-4 reveals key role of lysosomal sequestration and the proteasome complex in acquiring chemoresistance to cisplatin

MERLOS RODRIGO, M. BUCHTELOVÁ, H. DE LOS RIOS, V. CASAL ÁLVAREZ, J. ECKSCHLAGER, T. HRABĚTA, J. BELHAJOVÁ, M. HEGER, Z. ADAM, V.

Originální název

Proteomic signature of neuroblastoma cells UKF-NB-4 reveals key role of lysosomal sequestration and the proteasome complex in acquiring chemoresistance to cisplatin

Anglický název

Proteomic signature of neuroblastoma cells UKF-NB-4 reveals key role of lysosomal sequestration and the proteasome complex in acquiring chemoresistance to cisplatin

Jazyk

en

Originální abstrakt

Cisplatin (CDDP) is a widely used agent in the treatment of neuroblastoma. Unfortunately, the development of acquired chemoresistance limits its clinical use. To gain a detailed understanding of the mechanisms underlying the development of such chemoresistance, we comparatively analyzed established cisplatin-resistant neuroblastoma cell line (UKF-NB-4(CDDP)) and its sensitive counterpart (UKF-NB-4). First, using viability screenings, we confirmed the decreased sensitivity of tested cells to cisplatin and identified a cross-resistance to carboplatin and oxaliplatin. Then, the proteomic signatures were analyzed using nano liquid chromatography with tandem mass spectrometry. Among the proteins responsible for UKF-NB-4(CDDP) chemoresistance, ion channels transport family proteins, ATP-binding cassette superfamily proteins (ATP = adenosine triphosphate), solute carrier-mediated trans-membrane transporters, proteasome complex subunits, and V-ATPases were identified. Moreover, we detected markedly higher proteasome activity in UKF-NB-4(CDDP) cells and a remarkable lysosomal enrichment that can be inhibited by bafilomycin A to sensitize UKF-NB-4(CDDP) to CDDP. Our results indicate that lysosomal sequestration and proteasome activity may be one of the key mechanisms responsible for intrinsic chemoresistance of neuroblastoma to CDDP.

Anglický abstrakt

Cisplatin (CDDP) is a widely used agent in the treatment of neuroblastoma. Unfortunately, the development of acquired chemoresistance limits its clinical use. To gain a detailed understanding of the mechanisms underlying the development of such chemoresistance, we comparatively analyzed established cisplatin-resistant neuroblastoma cell line (UKF-NB-4(CDDP)) and its sensitive counterpart (UKF-NB-4). First, using viability screenings, we confirmed the decreased sensitivity of tested cells to cisplatin and identified a cross-resistance to carboplatin and oxaliplatin. Then, the proteomic signatures were analyzed using nano liquid chromatography with tandem mass spectrometry. Among the proteins responsible for UKF-NB-4(CDDP) chemoresistance, ion channels transport family proteins, ATP-binding cassette superfamily proteins (ATP = adenosine triphosphate), solute carrier-mediated trans-membrane transporters, proteasome complex subunits, and V-ATPases were identified. Moreover, we detected markedly higher proteasome activity in UKF-NB-4(CDDP) cells and a remarkable lysosomal enrichment that can be inhibited by bafilomycin A to sensitize UKF-NB-4(CDDP) to CDDP. Our results indicate that lysosomal sequestration and proteasome activity may be one of the key mechanisms responsible for intrinsic chemoresistance of neuroblastoma to CDDP.

Plný text v Digitální knihovně

http://hdl.handle.net/11012/195620

Dokumenty

BibTex 


@article{BUT156373,
  author="Miguel Ángel {Merlos Rodrigo} and Hana {Michálková} and Vivian {De los Rios} and José Ignacio {Casal Álvarez} and Tomáš {Eckschlager} and Jan {Hraběta} and Marie {Belhajová} and Zbyněk {Heger} and Vojtěch {Adam}",
  title="Proteomic signature of neuroblastoma cells UKF-NB-4 reveals key role of lysosomal sequestration and the proteasome complex in acquiring chemoresistance to cisplatin",
  annote="Cisplatin (CDDP) is a widely used agent in the treatment of neuroblastoma. Unfortunately, the development of acquired chemoresistance limits its clinical use. To gain a detailed understanding of the mechanisms underlying the development of such chemoresistance, we comparatively analyzed established cisplatin-resistant neuroblastoma cell line (UKF-NB-4(CDDP)) and its sensitive counterpart (UKF-NB-4). First, using viability screenings, we confirmed the decreased sensitivity of tested cells to cisplatin and identified a cross-resistance to carboplatin and oxaliplatin. Then, the proteomic signatures were analyzed using nano liquid chromatography with tandem mass spectrometry. Among the proteins responsible for UKF-NB-4(CDDP) chemoresistance, ion channels transport family proteins, ATP-binding cassette superfamily proteins (ATP = adenosine triphosphate), solute carrier-mediated trans-membrane transporters, proteasome complex subunits, and V-ATPases were identified. Moreover, we detected markedly higher proteasome activity in UKF-NB-4(CDDP) cells and a remarkable lysosomal enrichment that can be inhibited by bafilomycin A to sensitize UKF-NB-4(CDDP) to CDDP. Our results indicate that lysosomal sequestration and proteasome activity may be one of the key mechanisms responsible for intrinsic chemoresistance of neuroblastoma to CDDP.",
  address="American Chemical Society",
  chapter="156373",
  doi="10.1021/acs.jproteome.8b00867",
  howpublished="print",
  institution="American Chemical Society",
  number="3",
  volume="18",
  year="2019",
  month="march",
  pages="1255--1263",
  publisher="American Chemical Society",
  type="journal article in Web of Science"
}