The interaction of mast cells with membranes from lung cancer cells induces the release of extracellular vesicles with a unique miRNA signature

Abstract

Mast cells (MCs) are immune cells that play roles in both normal and abnormal processes. They have been linked to tumor progression in several types of cancer, including non-small cell lung cancer (NSCLC). However, the exact role of MCs in NSCLC is still unclear. Some studies have shown that the presence of a large number of MCs is associated with poor prognosis, while others have suggested that MCs have protective effects. To better understand the role of MCs in NSCLC, we aimed to identify the initial mechanisms underlying the communication between MCs and lung cancer cells. Here, we recapitulated cell-to-cell contact by exposing MCs to membranes derived from lung cancer cells and confirming their activation, as evidenced by increased phosphorylation of the ERK and AKT kinases. Profiling of the microRNAs that were selectively enriched in the extracellular vesicles (EVs) released by the lung cancer-activated MCs revealed that they contained significantly increased amounts of miR-100-5p and miR-125b, two protumorigenic miRNAs. We explored the pathways regulated by these miRNAs via enrichment analysis using the KEGG database, demonstrating that these two miRNAs regulate p53 signaling, cancer pathways, and pathways associated with apoptosis and the cell cycle.