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

Qu, Junle; Qu, Xiujuan; Zhao, Ming; Teng, Yingqi; Zhang, Y.; Hou, Kezuo; Jiang, Yong; Yang, Xiaoguang; Liu, Y.-P.

doi:10.1016/j.dld.2009.04.006

Cited by 268 publications

(209 citation statements)

References 29 publications

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“…It was identified that these exosomes induced the viability of 5637 and T24 cells in a time-and dose-dependent manner. These results are consistent with those of previous studies showing that breast and gastric cancer cell-released exosomes stimulated the proliferation of their parental cells in vitro (17,23). In addition, these results suggest that certain common molecular events or mechanisms may be responsible for tumor-derived exosomes in the promotion of cell proliferation and the suppression of apoptosis.…”

Section: Discussionsupporting

confidence: 83%

“…Previous studies have demonstrated that exosomes derived from tumor cells possess anti-tumor properties, such as inducing tumor cell apoptosis (12) and enhancing anti-tumor immunity (13). Exosomes have also been extensively studied as a novel cell-free source of tumor antigens to develop anti-cancer vaccines (14-15) However, it is increasingly suggested that exosomes may also affect tumor progression by exhibiting immunosuppressive properties, facilitating tumor invasion and metastasis, stimulating tumor cell proliferation or inducing drug resistance (16) A recent study showed that gastric cancer-derived exosomes promoted tumor cell proliferation and activated the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and lipid kinase phoshoinositide-3-kinase (PI3K)/Akt signaling pathways (17).…”

Section: Introductionmentioning

confidence: 99%

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Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro

Yang

Wang

et al. 2013

Molecular Medicine Reports

133

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Abstract. Exosomes are small membrane vesicles released by a variety of mammalian cells into the extracellular space and are involved in cell-to-cell signaling. This study aimed to investigate the effects of bladder cancer cell-derived exosomes on the regulation of tumor cell viability and apoptosis, as well as the underlying molecular events. Exosomes were purified from the supernatants of human bladder cancer T24 cell cultures. Transmission electron microscopy was used to confirm their morphology and western blot analyses determined the protein content of cells. Subsequently, bladder cancer cell lines were treated with different concentrations of exosomes. Tumor cell viability was shown to be reduced, as detected by the Cell Counting Kit-8 assay. Annexin V/flow cytometric assays showed that exosomes inhibited apoptosis of bladder cancer cell lines in a dose-and time-dependent manner. Exosomes were demonstrated to upregulate the expression of Bcl-2 and Cyclin D1 proteins, but reduce the levels of Bax and caspase-3 proteins in these cells. Moreover, exosomes dose-dependently increased the expression of phosphorylated Akt and extracellular signal-regulated protein kinase (ERK). In conclusion, this study demonstrated that bladder cancer cell-derived exosomes inhibited tumor cell apoptosis, which was associated with the activation of Akt and ERK pathway genes, suggesting that tumor-derived exosomes are involved in bladder cancer progression. Inhibition of exosome formation and release may therefore be a novel strategy in future treatment of bladder cancer.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro

Yang

Wang

et al. 2013

Molecular Medicine Reports

133

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“…Tumor-derived exosomes, or membrane-bound nanoparticles present in a tumor microenvironment, significantly influence extracellular signal transmission. Gastric cancer exosomes also promote tumor cell proliferation [10]. Our previous studies also showed that hepaCAM re-expression in renal cancer cells can significantly inhibit cell proliferation [12].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, exosomes may promote the proliferation of adjacent tumor cells. The effect of gastric cancer-derived exosomes on the proliferation of the released cells has been documented [10], but the exact mechanism of cell proliferation remains unclear. p-AKT, also called protein kinase B, mediates cell apoptosis and proliferation [11]; the overexpression of p-AKT may contribute to the development and progression of malignancies.…”

Section: Renal Tumor-derived Exosomes Inhibit Hepacam Expression Of Rmentioning

confidence: 99%

Renal tumor-derived exosomes inhibit hepaCAM expression of renal carcinoma cells in a p-AKT-dependent manner

Jiang¹,

Zhang²,

Tan³

et al. 2014

neo

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HepaCAM mediates cancer cell proliferation, migration and differentiation. Our previous studies showed the effects of hepaCAM on the inhibition of renal carcinoma cell proliferation. To further investigate the reason for the low expression of hepaCAM in renal carcinoma and the corresponding molecular mechanisms, we detected renal carcinoma OS-RC-2 cell lines containing high expression of hepaCAM; and hepaCAM and p-AKT were also detected in these cells. Exosomes were isolated and purified from the supernatant liquid of OS-RC-2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry analysis were conducted to determine the effect of exosomes on the proliferation and cycle distribution of OS-RC-2 cells. OS-RC-2 cells (high expression of hepaCAM) were treated with exosomes or plus MK-2206 (AKT inhibitor); and hepaCAM, AKT and p-AKT were detected in these cells by western blot analysis. The correlation between hepaCAM and p-AKT was analysed by immunohistochemical method. Results showed that hepaCAM re-expression in OS-RC-2 cell lines resulted in significant weakening of proliferation ability and more prominent G0/G1 population as well as reduction of p-AKT protein. The increase in proliferation caused by exosomes was followed by hepaCAM downregulation and p-AKT upregulation in OS-RC-2 cells (high expression of hepaCAM). By comparison, the promotion of proliferation caused by exosomes was weakened and hepaCAM expression changed after MK-2206 treatment; however, this change was not significant. HepaCAM was negatively correlated with p-AKT protein in renal cell carcinoma tissues. Therefore, renal tumor-derived exosomes may be an important factor resulting in the low expression of hepaCAM by upregulating p-AKT in renal carcinoma.

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“…In addition, there is accumulating evidence that two pathways may cooperate to promote the survival of transformed cells (33,(42)(43)(44), but the interactions among them remain to be resolved. Some studies indicated that ERK1/2 located downstream of Akt and overexpression of Akt apparently suppressed the phosphorylation of ERK1/2 (33,45,46).…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen-induced apoptosis of rat C6 glioma cells via PI3K/Akt, JNK and ERK activation

Feng

Huang²,

Ding³

et al. 2010

Oncol Rep

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Abstract.To elucidate the mechanism of TAM treatment on gliomas, we hypothesised that PI3K/Akt and MAPK signaling pathway may play important roles on TAM-induced apoptosis in C6 glioma cells. Our results demonstrated that TAM induced apoptosis of C6 glioma cells in a dose-dependent manner. The activation of AKT significantly decreased in a time-dependent manner in response to TAM treatment, JNK was transiently activated, and subsequently decreased activation and kept stable level, whereas ERK evidenced sustained activations in response to the drug treatment. The inhibition of PI3K/Akt and JNK both accelerated and enhanced TAM-induced apoptosis and ERK inhibition apparently exerted negative effect on apoptosis. We also observed that PI3K/Akt had intimate association with JNK and ERK activation in TAM-induced apoptosis. These findings may provide strategies for the molecularly targeted therapy in malignant gliomas.

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

Cited by 268 publications

References 29 publications

Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro

Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro

Renal tumor-derived exosomes inhibit hepaCAM expression of renal carcinoma cells in a p-AKT-dependent manner

Tamoxifen-induced apoptosis of rat C6 glioma cells via PI3K/Akt, JNK and ERK activation

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

Cited by 268 publications

References 29 publications

Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro

Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro

Renal tumor-derived exosomes inhibit hepaCAM expression of renal carcinoma cells in a p-AKT-dependent manner

Tamoxifen-induced apoptosis of rat C6 glioma cells via PI3K/Akt, JNK and ERK activation

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Renal tumor-derived exosomes inhibit hepaCAM expression of renal carcinoma cells in a p-AKT-dependent manner