M2 Macrophage-Derived Exosomes Promote Angiogenesis and Growth of Pancreatic Ductal Adenocarcinoma by Targeting E2F2.
M2 Macrophage-Derived Exosomes Promote Angiogenesis and Growth of Pancreatic Ductal Adenocarcinoma by Targeting E2F2.
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DOI：
10.1016/j.ymthe.2020.11.024
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发表时间：
2021-03-03
期刊：
影响因子：
--
通讯作者：
Qiu Z
中科院分区：
文献类型：
--
作者：
Yang Y;Guo Z;Chen W;Wang X;Cao M;Han X;Zhang K;Teng B;Cao J;Wu W;Cao P;Huang C;Qiu Z
胰腺导管腺癌（Pancreatic ductal adenocarcinoma，PDAC）是世界上最具侵袭性的肿瘤之一，预后差，其进展与血管密度呈正相关。最近，肿瘤相关巨噬细胞（TAMs）被证明是有益的血管生成，但其作用机制仍不清楚。我们的研究表明M2巨噬细胞与PDAC组织的微血管密度（MVD）呈正相关，M2巨噬细胞来源的exosomes（MDEs）在体外可促进小鼠主动脉内皮细胞（MAECs）的血管生成。同时，M2 MDES还能促进小鼠皮下肿瘤的生长，增加小鼠皮下血管密度。此外，我们还发现miR-155- 5 p和miR-221- 5 p在M2 MDE中的水平高于M0 MDE中的水平，并且它们可以转移到MAEC中，如RNA测序（RNA-seq）和qPCR分析所证明的。我们的数据证实了TAMs和PDAC的血管生成之间的相互作用。此外，靶向来自TAM的外泌体miRNA可能为PDAC提供诊断和治疗策略。在这项研究中，Qiu及其同事发现M2巨噬细胞来源的外泌体可以促进胰腺癌的血管生成，这揭示了肿瘤中巨噬细胞和血管内皮细胞之间通讯的新机制。本研究为胰腺癌的治疗提供了一个潜在的靶点。
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. In this study, Qiu and colleagues found that M2 macrophage-derived exosomes could promote angiogenesis in pancreatic cancer, which revealed a new mechanism of communication between macrophages and vascular endothelial cells in tumors. This study provides a potential therapeutic target for pancreatic cancer.
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影响因子：
4.8
作者：
Song, Xiao;Ding, Yanping;Nie, Guangjun
通讯作者：
Nie, Guangjun
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作者：
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通讯作者：
Chen W
影响因子：
9.8
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通讯作者：
Griffioen AW