Bottom up proteomics reveals novel differentiation proteins in neuroblastoma cells treated with 13-cis retinoic acid.

Abstract:

:Neuroblastoma, a cancer of the sympathetic nervous system, is the second most common pediatric cancer. A unique feature of neuroblastoma is remission in some patients due to spontaneous differentiation of metastatic tumors. 13-cis retinoic acid (13-cis RA) is currently used in the clinic to treat neuroblastoma due to its differentiation inducing effects. In this study, we used shotgun proteomics to identify proteins affected by 13-cis RA treatment in neuroblastoma SK-N-SH cells. Our results showed that 13-cis RA reduced proteins involved in extracellular matrix synthesis and organization and increased proteins involved in cell adhesion and neurofilament formation. These changes indicate that 13-cis RA induces tumor cell differentiation by decreasing extracellular matrix rigidity and increasing neurite overgrowth. Differentially-affected proteins identified in this study may be novel biomarkers of drug efficacy in the treatment of neuroblastoma. SIGNIFICANCE: As neuroblastoma can spontaneously differentiate, determining which proteins are involved in differentiation can guide development of novel treatments. 13-cis retinoic acid is currently used in the clinic as a differentiation inducer. Here we have established a proteome map of SK-N-SH cells treated with 13-cis retinoic acid. Bioinformatic analysis revealed the involvement of development, differentiation, extracellular matrix assembly, collagen biosynthesis, and neurofilament bundle association. This proteome map provides information as to which proteins are important for differentiation and identifies networks that can be targeted by drugs to treat neuroblastoma [1].

journal_name

J Proteomics

journal_title

Journal of proteomics

authors

Halakos EG,Connell AJ,Glazewski L,Wei S,Mason RW

doi

10.1016/j.jprot.2019.103491

subject

Has Abstract

pub_date

2019-10-30 00:00:00

pages

103491

eissn

1874-3919

issn

1876-7737

pii

S1874-3919(19)30263-5

journal_volume

209

pub_type

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