Tumor-associated macrophages secret exosomal miR-155 to promote metastasis of non-small-cell lung cancer

Abstract

Background: Understanding the molecular basis underlying metastasis of non-small-cell lung cancer (NSCLC) may provide new therapeutic modality for treatment of NSCLC. However, the mechanisms by which tumor-associated macrophages (TAMs) affect NSCLC metastasis still remain undefined. Method: Phenotype of TAMs was identified by flow cytometry. The migration of the tumor cells was detected by transwell assay. Transmission electron microscopy (TEM) and PKH-67 was used to identified and label the exosome. Expression of miR-155 was measured by qRT-PCR. Luciferase analysis, western blot, and rescue assay were used to investigate potential mechanisms of miR-155.Results: We discovered a novel regulatory pathway involved in NSCLC metastasis. We found that M2 TAMs were the main TAMs in metastatic tissues of NSCLC patients and exosomes derived from M2 TAMs were able to promote epithelial-mesenchymal transition (EMT) and migration of NSCLC cells. We demonstrated that miR-155 was abundant in M2 TAMs and exosomes secreted by M2 TAMs. Moreover, we also verified that miR-155 was the key functional biomolecule in exosomes secreted by M2 TAMs. Furthermore, we confirmed that deletion of miR-155 in M2 TAMs could significantly prevent NSCLC metastasis. Overall, Conclusions: we revealed a new regulatory pathway that is M2 TAMs secret exosomal miR-155 to promote NSCLC metastasis. Our findings may provide a practical target for treatment of NSCLC.