Details

Autor(en) / Beteiligte

• Merlos Rodrigo, Miguel Angel
• Buchtelova, Hana
• de los Rios, Vivian
• Casal, José Ignacio
• Eckschlager, Tomas
• Hrabeta, Jan
• Belhajova, Marie
• Heger, Zbynek
• Adam, Vojtech

Titel

Proteomic Signature of Neuroblastoma Cells UKF-NB‑4 Reveals Key Role of Lysosomal Sequestration and the Proteasome Complex in Acquiring Chemoresistance to Cisplatin

Ist Teil von

• Journal of proteome research, 2019-03, Vol.18 (3), p.1255-1263

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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-4CDDP) 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-4CDDP 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-4CDDP cells and a remarkable lysosomal enrichment that can be inhibited by bafilomycin A to sensitize UKF-NB-4CDDP 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.