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Protective role of mouse mast cell tryptase Mcpt6 in melanoma.

Research paper by Mirjana M Grujic, Lars L Hellman, Ann-Marie AM Gustafson, Srinivas S Akula, Fabio Rabelo FR Melo, Gunnar G Pejler

Indexed on: 04 Jan '20Published on: 03 Jan '20Published in: Pigment Cell & Melanoma Research



Abstract

Tryptase-positive mast cells populate melanomas but it is not known whether tryptase impacts on melanoma progression. Here we addressed this and show that melanoma growth is significantly higher in tryptase-deficient (Mcpt6 ) versus. wild-type mice. Histochemical analysis showed that mast cells were frequent in the tumor stroma of both wild-type and Mcpt6 mice, and also revealed their presence within the tumor parenchyma. Confocal microscopy analysis revealed that tryptase was taken up by the tumor cells. Further, tryptase-positive granules were released from mast cells and were widely distributed within the tumor tissue, suggesting that tryptase could impact on the tumor microenvironment. Indeed, gene expression analysis showed that the absence of Mcpt6 caused decreased expression of numerous genes, including Cxcl9, Tgtp2 and Gbp10, while the expression of 5p-miR3098 was enhanced. The levels of CXCL9 were lower in serum from Mcpt6 versus. wild-type mice. In further support of a functional impact of tryptase on melanoma, recombinant tryptase (Mcpt6) was taken up by cultured melanoma cells and caused reduced proliferation. Altogether, our results indicate a protective role of mast cell tryptase in melanoma growth. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.