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

X. L. JIANG, Y. ZHANG, B. TAN, C. L. LUO, X. H. WU

Abstract:

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.

Issue: 4/2014

Volume: 2014

Pages: 416 — 423

DOI: 10.4149/neo_2014_051

Pubmed

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