| Summary: | Although mast cells have been found in multiple malignancies, their functional contribution remains controversial. We found mast cells in mouse and human malignant pleural effusions, and studied their functions. Mouse adenocarcinomas competent of malignant effusions potently chemoattracted and subsequently degranulated mast cells in the thorax by releasing chemokine ligand 2 and osteopontin, respectively. Mast cells were essential for malignant pleural effusion formation, cooperating with tumor cells and the pleural environment to trigger vasoactive and oncotrophic effects upon tumor cell encounter. To achieve this, mast cells secreted tryptase AB1 and interleukin-1β, that, in turn, potently triggered vascular hypermeability and tumor cell nuclear factor-κΒ activation, respectively. cKIT inhibitor imatinib mesylate was effective against effusion development, indicating that mast cell-dependent effusion formation is actionable.
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