Chromogranin A regulates neuroblastoma proliferation and phenotype

Chromogranin A regulates neuroblastoma proliferation and phenotype

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Neuroblastoma is a commonly encountered solid tumor in early childhood with high neuroplasticity, and differentiation therapy is hypothesized to lead to tumor mass shrinkage and/or symptom relief.CgA is a tissue specific protein ivoryjinelle.com restricted to the diffuse neuroendocrine system, and widely expressed in neuroblastomas.Using knockdown and knockout approaches to deplete CgA levels, we demonstrated that CgA loss inhibits SH-SY5Y cell proliferation and leads to a morphological shift with increased expression of Schwann and extracellular matrix specific molecules, and suppression of chromaffin features.

We further confirmed the effects of CgA in a 2006 nissan altima radio series of neuroblastoma cells with [BE(2)-M17 and IMR-32] and without (SK-N-SH) N-Myc amplification.We demonstrated that CgA depletion reduced IGF-II and IGFBP-2 expression, increased IGFBP-3 levels, and suppresses IGF downstream signaling as evidenced by reduced AKT/ERK pathway activation.This was further supported by an increased anti-proliferative effect of the ERK inhibitor in the CgA depleted cells.

In an in vivo xenograft neuroblastoma model, CgA knockdown led to increased S-phenotypic marker expression at both protein and mRNA levels.Together these results suggest that CgA maintains IGF secretion and intracellular signaling to regulate proliferation and differentiation in neuroblastomas.