Protective role of mouse mast cell tryptase Mcpt6 in melanoma.

Grujic, Mirjana (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

Hellman, Lars (author): Uppsala universitet,Institutionen för cell- och molekylärbiologi

Gustafson, Ann-Marie (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

Akula, Srinivas (author)

Melo, Fabio Rabelo (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

Pejler, Gunnar (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

(creator_code:org_t)

2020-01-19
2020
English.
In: Pigment Cell & Melanoma Research. - : Wiley. - 1755-1471 .- 1755-148X. ; 33:4, s. 579-590

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Abstract Subject headings

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.

By the author/editor: Grujic, Mirjana; Hellman, Lars; Gustafson, Ann-M ...; Akula, Srinivas; Melo, Fabio Rabe ...; Pejler, Gunnar

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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