Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation
Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation
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胃癌外泌体通过 PI3K/Akt 和 MAPK/ERK 激活促进肿瘤细胞增殖
DOI:
10.1016/j.dld.2009.04.006
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发表时间:
2009-12-01
影响因子:
4.5
通讯作者:
Liu, Y. -P
中科院分区:
文献类型:
--
作者:
Qu, J. -L.;Qu, X. -J.;Liu, Y. -P
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 turnout 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. (C) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.