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Protective role of mouse mast cell tryptase Mcpt6 in melanoma

Grujic, Mirjana and Hellman, Lars and Gustafson, Ann-Marie and Akula, Srinivas and Melo, Fabio Rabelo and Pejler, Gunnar (2020). Protective role of mouse mast cell tryptase Mcpt6 in melanoma. Pigment Cell and Melanoma Research. 33 , 579-590
[Journal article]

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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.

Authors/Creators:Grujic, Mirjana and Hellman, Lars and Gustafson, Ann-Marie and Akula, Srinivas and Melo, Fabio Rabelo and Pejler, Gunnar
Title:Protective role of mouse mast cell tryptase Mcpt6 in melanoma
Year of publishing :2020
Volume:33
Page range:579-590
Number of Pages:12
Publisher:John Wiley & Sons Ltd
ISSN:1755-1471
Language:English
Publication Type:Journal article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Cell and Molecular Biology
Keywords:CXCL9, mast cells, Mcpt6, melanoma, tryptase
URN:NBN:urn:nbn:se:slu:epsilon-p-104041
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-104041
Additional ID:
Type of IDID
DOI10.1111/pcmr.12859
Web of Science (WoS)000507908100001
ID Code:17365
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
Deposited By: SLUpub Connector
Deposited On:01 Sep 2020 12:34
Metadata Last Modified:01 Sep 2020 12:34

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