PMID- 30419348 OWN - NLM STAT- MEDLINE DCOM- 20191101 LR - 20191101 IS - 1872-7980 (Electronic) IS - 0304-3835 (Linking) VI - 442 DP - 2019 Feb 1 TI - Exosomes derived from human umbilical cord mesenchymal stromal cells deliver exogenous miR-145-5p to inhibit pancreatic ductal adenocarcinoma progression. PG - 351-361 LID - S0304-3835(18)30660-8 [pii] LID - 10.1016/j.canlet.2018.10.039 [doi] AB - The roles of miRNAs in the development of cancer have made them promising tools for novel therapeutic approaches. However, the successful delivery of miRNAs to cancer cells has been hampered by difficulties in developing an effective and sustainable delivery mechanism. Exosomes are small endogenous membrane vesicles that mediate communication between cells by delivering genetic materials. Thus, given their intrinsic properties, exosomes have been a focus for use as biological delivery vehicles for miRNAs transfer. Whether exosomes can effectively deliver exogenous miRNAs to pancreatic ductal adenocarcinoma (PDAC) cells has not been thoroughly investigated. Here, we used exosomes from human umbilical cord mesenchymal stromal cells (hucMSCs) to deliver exogenous miR-145-5p, which inhibited PDAC cell proliferation and invasion and increased apoptosis and cell cycle arrest, concomitant with decreased Smad3 expression in vitro. Using a mouse model, we also demonstrated that overexpressing miR-145-5p significantly reduced the growth of xenograft tumors in vivo. Our findings provide novel insights that exosomes might be an attractive therapeutic vehicle for the clinical administration of miRNAs in patients with PDAC. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Ding, Yixuan AU - Ding Y AD - Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. FAU - Cao, Feng AU - Cao F AD - Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. FAU - Sun, Haichen AU - Sun H AD - Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. FAU - Wang, Yecheng AU - Wang Y AD - Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. FAU - Liu, Shuang AU - Liu S AD - Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. FAU - Wu, Yanchuan AU - Wu Y AD - Department of Central Laboratory, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. FAU - Cui, Qingye AU - Cui Q AD - Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. FAU - Mei, WenTong AU - Mei W AD - Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. FAU - Li, Fei AU - Li F AD - Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. Electronic address: lifei20180619@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181109 PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Antigens, CD) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (CDH1 protein, human) RN - 0 (CDH2 protein, human) RN - 0 (Cadherins) RN - 0 (MIRN145 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (SMAD3 protein, human) RN - 0 (Smad3 Protein) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - Apoptosis MH - Apoptosis Regulatory Proteins/metabolism MH - Cadherins/metabolism MH - Carcinoma, Pancreatic Ductal/genetics/metabolism/pathology/*therapy MH - Cell Cycle Checkpoints MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Exosomes/genetics/metabolism/*transplantation/ultrastructure MH - Humans MH - Male MH - *Mesenchymal Stem Cells/metabolism/ultrastructure MH - Mice, Inbred BALB C MH - Mice, Nude MH - MicroRNAs/genetics/*metabolism MH - Neoplasm Invasiveness MH - Pancreatic Neoplasms/genetics/metabolism/pathology/*therapy MH - Smad3 Protein/metabolism MH - Tumor Burden MH - Umbilical Cord/*cytology MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - Exosomes OT - HucMSC OT - MiR-145-5p OT - PDAC OT - Treatment EDAT- 2018/11/13 06:00 MHDA- 2019/11/02 06:00 CRDT- 2018/11/13 06:00 PHST- 2018/06/21 00:00 [received] PHST- 2018/09/14 00:00 [revised] PHST- 2018/10/25 00:00 [accepted] PHST- 2018/11/13 06:00 [pubmed] PHST- 2019/11/02 06:00 [medline] PHST- 2018/11/13 06:00 [entrez] AID - S0304-3835(18)30660-8 [pii] AID - 10.1016/j.canlet.2018.10.039 [doi] PST - ppublish SO - Cancer Lett. 2019 Feb 1;442:351-361. doi: 10.1016/j.canlet.2018.10.039. Epub 2018 Nov 9.