Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Qu
J-L
JL
Department of Medical Oncology, The First Hospital, China Medical University, NO 155, North Nanjing Street, Heping District, Shenyang City 110001, China.
Qu
X-J
XJ
Zhao
M-F
MF
Teng
Y-E
YE
Zhang
Y
Y
Hou
K-Z
KZ
Jiang
Y-H
YH
Yang
X-H
XH
Liu
Y-P
YP
D015153:Blotting, Western; D049109:Cell Proliferation; D055354:Exosomes / Q000201:enzymology*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases