Inuwa, RF, Moss, D, Quayle, J and Swadi, R (2024) Epac activation reduces trans-endothelial migration of undifferentiated neuroblastoma cells and cellular differentiation with a CDK inhibitor further enhances Epac effect. PloS one, 19 (11).

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Abstract

Neuroblastoma (NB) is the most common solid extracranial neoplasm found in children and is derived from primitive sympathoadrenal neural precursor. The disease accounts for 15% of all cancer deaths in children. The mortality rate is high in patients presenting with a metastatic tumour even with extensive treatments. This signifies the need for further research towards the development of new additional therapies that can combat not only tumour growth but metastasis, especially amongst the high-risk groups. During metastasis, primary tumour cells become migratory and travel towards a capillary within the tumour. They then degrade the matrix surrounding the pericytes and endothelial cells traversing the endothelial barrier twice to establish a secondary. This led to the hypothesis that modulation of the endothelial cell junctional stability could have an influence on tumour metastasis. To test this hypothesis, agents that modulate endothelial permeability on NB cell line migration and invasion were assessed in vitro in a tissue culture model. The cAMP agonist and its antagonists were found to have no obvious effect on both SK-N-BE2C and SK-N-AS migration, invasion and proliferation. Next, NB cells were cocultured with HDMEC cells and live cell imaging was used to assess the effect of an Epac agonist on trans-endothelial cell migration of NB cells. Epac1 agonist remarkably reduced the trans-endothelial migration of both SK-N-BE2C and SK-N-AS cells. These results demonstrate that an Epac1 agonist may perhaps serve as an adjuvant to currently existing therapies for the high-risk NB patients.

Item Type:	Article
Uncontrolled Keywords:	Cell Line, Tumor; Endothelial Cells; Humans; Neuroblastoma; Guanine Nucleotide Exchange Factors; Cyclic AMP; Protein Kinase Inhibitors; Cell Differentiation; Cell Movement; Transendothelial and Transepithelial Migration; Humans; Guanine Nucleotide Exchange Factors; Neuroblastoma; Cell Line, Tumor; Cell Differentiation; Protein Kinase Inhibitors; Cell Movement; Transendothelial and Transepithelial Migration; Endothelial Cells; Cyclic AMP; General Science & Technology
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	Public Library of Science (PLoS)
SWORD Depositor:	A Symplectic
Date Deposited:	05 Nov 2024 15:53
Last Modified:	05 Nov 2024 16:00
DOI or ID number:	10.1371/journal.pone.0304547
Editors:	Horowitz, A
URI:	https://researchonline.ljmu.ac.uk/id/eprint/24678

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