PMID- 33221435 OWN - NLM STAT- MEDLINE DCOM- 20211118 LR - 20220304 IS - 1525-0024 (Electronic) IS - 1525-0016 (Print) IS - 1525-0016 (Linking) VI - 29 IP - 3 DP - 2021 Mar 3 TI - M2 Macrophage-Derived Exosomes Promote Angiogenesis and Growth of Pancreatic Ductal Adenocarcinoma by Targeting E2F2. PG - 1226-1238 LID - S1525-0016(20)30622-5 [pii] LID - 10.1016/j.ymthe.2020.11.024 [doi] AB - Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive tumors all over the world, has a generally poor prognosis, and its progression is positively correlated with the density of blood vessels. Recently, tumor-associated macrophages (TAMs) were proven to be beneficial for angiogenesis, but their mechanism of action remains unclear. Our study indicated that M2 macrophages were positively correlated with the microvessel density (MVD) of PDAC tissues, and M2 macrophage-derived exosomes (MDEs) could promote the angiogenesis of mouse aortic endothelial cells (MAECs) in vitro. At the same time, the M2 MDEs could also promote the growth of subcutaneous tumors and increase the vascular density of mice. Moreover, we also found that miR-155-5p and miR-221-5p levels in the M2 MDEs were higher than those in M0 MDEs, and they could be transferred into MAECs, as demonstrated by RNA sequencing (RNA-seq) and qPCR analysis. Our data confirmed the interaction between TAMs and the angiogenesis of PDAC by exosomes. Additionally, targeting the exosomal miRNAs derived from TAMs might provide diagnostic and therapeutic strategies for PDAC. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Yang, Yuhan AU - Yang Y AD - Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. FAU - Guo, Zengya AU - Guo Z AD - Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. FAU - Chen, Weiwei AU - Chen W AD - Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. FAU - Wang, Xiaofeng AU - Wang X AD - Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. FAU - Cao, Meng AU - Cao M AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. FAU - Han, Xuan AU - Han X AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. FAU - Zhang, Kundong AU - Zhang K AD - Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. FAU - Teng, Buwei AU - Teng B AD - Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, People's Republic of China. FAU - Cao, Jun AU - Cao J AD - Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. FAU - Wu, Weidong AU - Wu W AD - Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. FAU - Cao, Peng AU - Cao P AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. Electronic address: cao_peng@njucm.edu.cn. FAU - Huang, Chen AU - Huang C AD - Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. Electronic address: richard-hc@sohu.com. FAU - Qiu, Zhengjun AU - Qiu Z AD - Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. Electronic address: qiuzjdoctor@sina.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201120 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 RN - 0 (E2F2 Transcription Factor) RN - 0 (E2F2 protein, human) RN - 0 (MIRN155 microRNA, human) RN - 0 (MIRN221 microRNA, human) RN - 0 (MicroRNAs) SB - IM CIN - Mol Ther. 2021 Mar 3;29(3):895-896. PMID: 33600771 MH - Animals MH - Apoptosis MH - Carcinoma, Pancreatic Ductal/blood supply/immunology/*pathology MH - Cell Proliferation MH - E2F2 Transcription Factor/*antagonists & inhibitors MH - Endothelial Cells/immunology MH - Exosomes/*immunology MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Macrophages/*immunology MH - Male MH - Mice MH - Mice, Nude MH - MicroRNAs/genetics MH - Neovascularization, Pathologic/immunology/*pathology MH - Pancreatic Neoplasms/blood supply/immunology/*pathology MH - Prognosis MH - Tumor Cells, Cultured MH - Xenograft Model Antitumor Assays PMC - PMC7934635 COIS- Declaration of Interests The authors declare no competing interests. EDAT- 2020/11/23 06:00 MHDA- 2021/11/19 06:00 PMCR- 2022/03/03 CRDT- 2020/11/22 20:34 PHST- 2020/01/23 00:00 [received] PHST- 2020/08/28 00:00 [revised] PHST- 2020/11/15 00:00 [accepted] PHST- 2020/11/23 06:00 [pubmed] PHST- 2021/11/19 06:00 [medline] PHST- 2020/11/22 20:34 [entrez] PHST- 2022/03/03 00:00 [pmc-release] AID - S1525-0016(20)30622-5 [pii] AID - 10.1016/j.ymthe.2020.11.024 [doi] PST - ppublish SO - Mol Ther. 2021 Mar 3;29(3):1226-1238. doi: 10.1016/j.ymthe.2020.11.024. Epub 2020 Nov 20.