Neutral Sphingomyelinase 2 (nSMase2)-dependent Exosomal Transfer of Angiogenic MicroRNAs Regulate Cancer Cell Metastasis

被引：641

作者：

Kosaka, Nobuyoshi ^{[1
]}

Iguchi, Haruhisa ^{[1
,2
]}

Hagiwara, Keitaro ^{[1
,3
]}

Yoshioka, Yusuke ^{[1
]}

Takeshita, Fumitaka ^{[1
]}

Ochiya, Takahiro ^{[1
]}

机构：

[1] Natl Canc Ctr, Res Inst, Div Mol & Cellular Med, Chuo Ku, Tokyo 1040045, Japan

[2] Dainippon Sumitomo Pharma Co Ltd, Pharmacol Res Labs, Konohana Ku, Osaka 5540022, Japan

[3] Tokyo Inst Technol, Dept Biol Informat, Grad Sch Biosci & Biotechnol, Yokohama, Kanagawa 2268501, Japan

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2013年 / 288卷 / 15期

基金：

日本学术振兴会;

关键词：

MECHANISMS; HYPOXIA; RNA;

D O I：

10.1074/jbc.M112.446831

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The release of humoral factors between cancer cells and the microenvironmental cells is critical for metastasis; however, the roles of secreted miRNAs in non-cell autonomous cancer progression against microenvironmental cells remain largely unknown. Here, we demonstrate that the neutral sphyngomyelinase 2 (nSMase2) regulates exosomal microRNA (miRNA) secretion and promotes angiogenesis within the tumor microenvironment as well as metastasis. We demonstrate a requirement for nSMase2-mediated cancer cell exosomal miRNAs in the regulation of metastasis through the induction of angiogenesis in inoculated tumors. In addition, miR-210, released by metastatic cancer cells, was shown to transport to endothelial cells and suppress the expression of specific target genes, which resulted in enhanced angiogenesis. These findings suggest that the horizontal transfer of exosomal miRNAs from cancer cells can dictate the microenviromental niche for the benefit of the cancer cell, like "on demand system" for cancer cells.

引用

页码：10849 / 10859

页数：11

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