Background: Exosomes are nanometer-sized vesicles that are released by normal and neoplastic cells. Previous studies have focused on the interaction between tumour-derived exosomes and the immune system, as a consequence of immune suppression or enhancement. However, the effects of tumour-derived exosomes on tumour cells themselves have not been well studied. Aims: To investigate the effects of gastric cancer exosomes on tumour cell proliferation and the possible mechanisms. Methods: By serial centrifugation and sucrose gradient ultracentrifugation, we isolated and purified the exosomes from gastric cancer SGC7901 cells, then viewed them by electron microscopy. Cell proliferation was measured by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay. Protein expression was assayed by Western blotting. Results: SGC7901-cell-derived exosomes promoted the proliferation of SGC7901 and BGC823 cells. The increase in proliferation induced by exosomes was accompanied by activation of Akt and extracellular-regulated protein kinase, and phosphoinositide 3-kinase or extracellular-regulated protein kinase inhibitor partially reversed the proliferative effect of exosomes. Moreover, the exosome-induced increase in activity of Akt and extracellular-regulated protein kinase coincided with decreased expression of the Casitas B-lineage lymphoma family of ubiquitin ligases. Conclusion: Gastric cancer exosomes promoted tumour cell proliferation, at least in part, by activation of PI3K/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinase pathways. The decreased expression of Casitas B-lineage lymphoma proteins might have contributed to the activation of Akt and extracellular-regulated protein kinase. © 2009 Editrice Gastroenterologica Italiana S.r.l.
CITATION STYLE
Qu, J. L., Qu, X. J., Zhao, M. F., Teng, Y. E., Zhang, Y., Hou, K. Z., … Liu, Y. P. (2009). Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation. Digestive and Liver Disease, 41(12), 875–880. https://doi.org/10.1016/j.dld.2009.04.006
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