Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells
Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells
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DOI：
10.1016/j.bbagrm.2014.09.002
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发表时间：
2014-11-01
影响因子：
4.7
通讯作者：
Akao, Yuldhiro
中科院分区：
文献类型：
--
作者：
Yamada, Nami;Tsujimura, Nonoka;Akao, Yuldhiro
关于循环microrna （mirna）或微囊泡（mv）的新研究表明它们有潜力成为新的生物标志物和癌症治疗靶点。然而，这些mirna和mv的生物学作用尚未得到证实。为了确定MV的生物学意义，我们以人类结直肠癌细胞作为MV供体，内皮细胞（HUVECs）作为MV受体，展示了结直肠癌细胞衍生的MV （crc -MV）向HUVECs的转移，并评估了这些MV及其货物在肿瘤血管生成中的作用。因此，与crc - mv孵育的HUVECs促进了这些细胞的增殖、迁移和成管活性。miR-1246和tgf - β被认为通过激活huvec中的Smad 1/5/8信号，负责MVs的促血管生成功能。这些结果提示结直肠癌细胞分泌mv参与肿瘤血管生成。(C) 2014 Elsevier B.V.版权所有
Emerging studies on circulating microRNAs (miRNAs) or microvesicles (MVs) have shown the potential of them to be novel biomarkers and therapeutic targets for cancer. However, the biological roles of these miRNAs and MVs have not been validated yet. To determine the biological significance of MVs, we used human colorectal cancer cells as the MV donor and endothelial cells (HUVECs) as the MV recipient and demonstrated the transfer of colorectal cancer cell-derived MVs (CRC-MVs) to HUVECs and evaluated the roles of these MVs and their cargo in tumor angiogenesis. Consequently, the incubation of HUVECs with CRC-MVs promoted the proliferation, migration, and tube formation activities of these cells. Among the cargoes shuttled by the MVs, miR-1246 and TGF-beta were considered to be responsible for the pro-angiogenic function of MVs by activating Smad 1/5/8 signaling in the HUVECs. These results suggest that colorectal cancer cells secreted MVs to contribute to tumor angiogenesis. (C) 2014 Elsevier B.V. All rights reserved.