1. Epac activation reduces trans-endothelial migration of undifferentiated neuroblastoma cells and cellular differentiation with a CDK inhibitor further enhances Epac effect.
- Author
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Inuwa RF, Moss D, Quayle J, and Swadi R
- Subjects
- Humans, Cell Line, Tumor, Protein Kinase Inhibitors pharmacology, Cell Movement drug effects, Transendothelial and Transepithelial Migration drug effects, Endothelial Cells drug effects, Endothelial Cells metabolism, Endothelial Cells pathology, Cyclic AMP metabolism, Guanine Nucleotide Exchange Factors metabolism, Guanine Nucleotide Exchange Factors antagonists & inhibitors, Neuroblastoma pathology, Neuroblastoma drug therapy, Neuroblastoma metabolism, Cell Differentiation drug effects
- 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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright: © 2024 Inuwa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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