title: Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis.
abstract: 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.
authors: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors: Nobuyoshi
authors: N
authors: Kosaka
authors: Haruhisa
authors: H
authors: Iguchi
authors: Keitaro
authors: K
authors: Hagiwara
authors: Yusuke
authors: Y
authors: Yoshioka
authors: Fumitaka
authors: F
authors: Takeshita
authors: Takahiro
authors: T
authors: Ochiya
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: C543800:MIRN210 microRNA, human; C549325:MIRN210 microRNA, mouse; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C491484:SMPD3 protein, human; C491483:Smpd3 protein, mouse; D013108:Sphingomyelin Phosphodiesterase