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.