Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 288, Issue 15, Pages 10849-10859Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.446831
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- Ministry of Education, Culture, Sports, Science, and Technology
- National Institute of Biomedical Innovation (NiBio)
- Japan Society for the Promotion of Science initiated by the Council for Science and Technology Policy
- Japanese Ministry of Education, Culture, Sports, Science, and Technology
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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.
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