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Zhang D, Babayan L, Ho H, et al. Chromogranin A regulates neuroblastoma proliferation and phenotype. Biol Open. 2019;8(3)doi: 10.1242/bio.036566.
Zhang, D., Babayan, L., Ho, H., & Heaney, A. P. (2019). Chromogranin A regulates neuroblastoma proliferation and phenotype. Biology open, 8(3), . https://doi.org/10.1242/bio.036566
Zhang, Dongyun, et al. "Chromogranin A regulates neuroblastoma proliferation and phenotype." Biology open vol. 8,3 (2019). doi: https://doi.org/10.1242/bio.036566
Zhang D, Babayan L, Ho H, Heaney AP. Chromogranin A regulates neuroblastoma proliferation and phenotype. Biol Open. 2019 Mar 04;8(3). doi: 10.1242/bio.036566. PMID: 30833285; PMCID: PMC6451332.
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Biol Open. 2019 Mar 04;8(3). doi: 10.1242/bio.036566.

Chromogranin A regulates neuroblastoma proliferation and phenotype.

Biology open

Dongyun Zhang, Lilit Babayan, Hillary Ho, Anthony P Heaney

Affiliations

  1. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles 90095, USA.
  2. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles 90095, USA [email protected].
  3. Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles 90095, USA.

PMID: 30833285 PMCID: PMC6451332 DOI: 10.1242/bio.036566

Abstract

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 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 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

© 2019. Published by The Company of Biologists Ltd.

Keywords: Chromogranin A; Differentiation therapy; Insulin-like growth factor; Neuroblastoma

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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