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Cancer Lett. 2016 Jun 1;375(2):331-339. doi: 10.1016/j.canlet.2016.03.026. Epub 2016 Mar 18.

Cell-derived microvesicles mediate the delivery of miR-29a/c to suppress angiogenesis in gastric carcinoma.

Author information

1
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
2
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
3
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Electronic address: dingzhih72@163.com.
4
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Electronic address: yingguoguang163@163.com.
5
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Electronic address: bayi@tjmuch.com.

Abstract

Microvesicles (MVs) secreted from cells have been found to mediate signal transduction between cells. In the tumor microenvironment, VEGF released from cancer cells plays a key role in promoting tumor angiogenesis. In this study, we characterized the inhibitory effect of MV-delivered miR-29a/c on angiogenesis and tumor growth in gastric cancer (GC). We found that the downregulation of miR-29a/c increases VEGF expression and release in GC cells, promoting the growth of vascular cells. By simulating the tumor microenvironment, the MV-delivered miR-29a/c significantly suppresses VEGF expression in GC cells, inhibiting vascular cell growth, metastasis, and tube formation. We also used a tumor implantation mouse model to show that secreted MVs containing overexpressed miR-29a/c significantly reduced the growth rate of the vasculature and tumors in vivo. To conclude, our results contribute to a novel anti-cancer strategy using miRNA-containing MVs to control tumor cell growth by blocking angiogenesis.

KEYWORDS:

Angiogenesis; Gastric cancer; Microvesicle; VEGF; miR-29

PMID:
27000664
DOI:
10.1016/j.canlet.2016.03.026
[Indexed for MEDLINE]

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