Protective role of mouse mast cell tryptase Mcpt6 in melanoma

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.

Keywords

CXCL9; mast cells; Mcpt6; melanoma; tryptase

Published in

Pigment Cell and Melanoma Research
2020, Volume: 33, number: 4, pages: 579-590 Publisher: WILEY

SLU Authors

• Pejler, Gunnar

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • Uppsala University

UKÄ Subject classification

Cell and Molecular Biology


Publication identifier

DOI: https://doi.org/10.1111/pcmr.12859

Permanent link to this page (URI)

https://res.slu.se/id/publ/104041