Research Paper
Exosomal miR-15b-5p derived from gastric cancer cells enhances immune infiltrating of tumor-associated macrophages through the WIF1/WNT5A axis
- 1 Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China
- 2 Department of Health Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China
Received: December 28, 2020 Accepted: May 13, 2021
https://doi.org/10.18632/aging.203192How to Cite
Copyright: © 2021 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: We intend to investigate the effects of gastric cancer (GC) cell-derived exosomes on tumor-associated macrophages (TAMs) and angiogenesis of vascular endothelial cells (VECs).
Methods: The exosomes from GC cells were extracted using the ultracentrifugation method. TAMs were treated with the exosomes and then co-cultured with GC cells or VECs. The viability, migration, invasion and apoptosis of GC cells were detected by the cell counting kit-8 (CCK-8) assay, transwell assay and flow cytometry, respectively. Meanwhile, the tube formation ability and viability of VECs were determined. Furthermore, gain- or loss- of function assays of miR-15b-5p were performed to probe its role in modulating the polarization of TAMs.
Results: TAMs significantly promoted GC cell proliferation, migration and invasion and repressed apoptosis. Additionally, TAMs promoted VECs’ angiogenesis. Forced overexpression of miR-15b-5p in GC cell-derived exosomes enhanced the "M2" polarization of TAMs. Moreover, TAMs with overexpressed-miR-15b-5p strengthened the malignant phenotypes of GC cells and increased the angiogenesis of VECs. Further mechanism studies showed that miR-15b-5p targeted and inhibited WIF1 and up-regulated WNT5A.
Conclusions: Exosomal miR-15b-5p shuttled by GC cells facilitated the “M2” polarization of TAMs by regulating the WIF1/WNT5A pathway, thus promoting GC progression.