Bottom up proteomics identifies neuronal differentiation pathway networks activated by cathepsin inhibition treatment in neuroblastoma cells that are enhanced by concurrent 13-cis retinoic acid treatment.

Autor: Halakos EG; Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA; Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA., Connell AJ; Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA., Glazewski L; Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA., Wei S; Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA., Mason RW; Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA; Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA. Electronic address: RobMason@udel.edu.
Jazyk: angličtina
Zdroj: Journal of proteomics [J Proteomics] 2021 Feb 10; Vol. 232, pp. 104068. Date of Electronic Publication: 2020 Dec 02.
DOI: 10.1016/j.jprot.2020.104068
Abstrakt: Neuroblastoma is the second most common pediatric cancer involving the peripheral nervous system in which stage IVS metastatic tumors regress due to spontaneous differentiation. 13-cis retinoic acid (13-cis RA) is currently used in the clinic for its differentiation effects and although it improves outcomes, relapse is seen in half of high-risk patients. Combinatorial therapies have been shown to be more effective in oncotherapy and since cathepsin inhibition reduces tumor growth, we explored the potential of coupling 13-cis RA with a cathepsin inhibitor (K777) to enhance therapeutic efficacy against neuroblastoma. Shotgun proteomics was used to identify proteins affected by K777 and dual (13-cis RA/K777) treatment in neuroblastoma SK-N-SH cells. Cathepsin inhibition was more effective in increasing proteins involved in neuronal differentiation and neurite outgrowth than 13-cis RA alone, but the combination of both treatments enhanced the neuronal differentiation effect. SIGNIFICANCE: As neuroblastoma can spontaneously differentiate, determining which proteins are involved in differentiation can guide development of more accurate diagnostic markers and more effective treatments. In this study, we established a differentiation proteomic map of SK-N-SH cells treated with a cathepsin inhibitor (K777) and K777/13-cis RA (dual). Bioinformatic analysis revealed these treatments enhanced neuronal differentiation and axonogenesis pathways. The most affected proteins in these pathways may become valuable biomarkers of efficacy of drugs designed to enhance differentiation of neuroblastoma [1].
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: