Mast cells act as partners in tumour cells metastasis to promote angiogenesis via exosomes

Abstract

Cancer cells release exosomes containing mRNA, miRNA and specific proteins. Exosomes can be taken up by mast cell, but the potential functional effects of mast cell on tumour metastasis remain unknown. Exosomes were isolated from the Lung adenocarcinoma cell line, A549, and uptake of PKH26-labelled exosomes by bone marrow mast cell, was examined using flow cytometry and fluorescence microscopy. The cytokines and typtase of mast cell supernatant was analyzed with Elisa kit and presence of typtase was determined by western blot. The cell proliferation and migration was determined CCK-8 and transwell. The proteins in the typtase-JAK-STAT signaling pathway were detected by Western blot. Mouse lung cancer model was then developed to observe the effect of lung cancer cell exosomes on formation and distant metastasis of primary tumors in vivo. Here we show that exosomes from A549 cells can be taken up by mast cells. Furthermore, A549 exosomes contain and transfer SCF protein to mast cells and subsequently induced mast cell activation through SCF-KIT signal transduction, which lead to degranulation of mast cells and release of tryptase. The tryptase accelerate the proliferation and migration in the human umbilical vein endothelial cells through the JAK-STAT signalling pathway. Our work identifies a mechanism for metastasis that exosomes can transfer SCF to active the mast cells, which can affect the release of the tryptase and then angiogenesis of human umbilical vein endothelial cells.