Pancreatic cancer-derived exosomal miR-510 promotes macrophage M2 polarization and facilitates cancer cell aggressive phenotypes

被引：0

作者：

Tao Wang ^{[1
]}

Lin Ye ^{[1
]}

Yingjie Zhou ^{[1
]}

Xionghan Zhang ^{[1
]}

Renjian Li ^{[1
]}

Yi Zhou ^{[1
]}

Jun Weng ^{[1
]}

Qingrong Mo ^{[1
]}

Yaqun Yu ^{[1
]}

机构：

[1] Affiliated Hospital of Guilin Medical University,Department of Hepatobiliary and Pancreatic Surgery

来源：

Human Cell | / 38卷 / 1期

关键词：

Pancreatic cancer (PC); miR-510; macrophage M2 polarization; STAT signaling;

D O I：

10.1007/s13577-024-01144-0

中图分类号：

学科分类号：

摘要：

Extensive tumor microenvironment (TME) and tumor-associated macrophages (TAMs) contribute to the initiation and progression of pancreatic cancer (PC). Cancer cell-derived exosomal miRNAs that stimulate macrophage M2 polarization might play an important role in the process. In the current study, we observed significant upregulation of miR-510 in PC cell lines in comparison to normal HPDE cell line, with PANC-1 exhibiting the highest and MIA PaCa-2 the lowest miR-510 levels. Functional assays demonstrated that miR-510 overexpression enhanced, while its inhibition reduced, PC cell viability, migration, invasion, and EMT. In vivo, miR-510 mimics promoted tumor growth and macrophage M2 polarization, whereas miR-510 inhibition had the opposite effect. Exosomes from PANC-1 and MIA PaCa-2 cells, characterized by nanoparticle tracking analysis and TEM, contained significantly higher miR-510 levels than those from HPDE cells. Macrophages incubated with conditioned media from these PC cells showed increased M2 polarization markers, a process inhibited by the exosome inhibitor GW4869. The delivery of miR-510 via PC cell-derived exosomes facilitated macrophage M2 polarization and regulated the STAT signaling pathway, suggesting that exosomal miR-510 plays a crucial role in the tumor microenvironment of PC by modulating macrophage M2 polarization.

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