Mast Cells Selectively Deliver Extracellular Vesicle-Encapsulated mRNA to Colorectal Cancer Cells.

Mast cells (MCs), a type of granulocytic immune cell, exert contrasting effects on tumorigenesis. The anti- or pro-tumorigenic activity of MCs depends on the cancer type, tumor microenvironment, and MC localization within the tumor. Consequently, their role remains controversial and poorly understood across multiple cancer types, including colorectal cancer (CRC). Most proposed mechanisms underlying MC activity in CRC have focused on MC secretion of biological factors. In this study, we demonstrated that MCs transfer extracellular vesicles containing mRNAs and proteins to CRC cells. This process occurs through a tightly regulated mechanism that requires direct cell-cell contact, calcium signaling, and integrin-mediated interactions. Such requirements resemble aspects of immunological synapses observed between lymphocytes and cancer cells. The novel mode of intercellular communication between MCs and cancer cells described here may help refine our understanding of MC functions in cancer biology.