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.

中文翻译：

---

小鼠肥大细胞类胰蛋白酶Mcpt6在黑色素瘤中的保护作用。

类胰蛋白酶阳性的肥大细胞遍布黑色素瘤，但尚不清楚类胰蛋白酶是否会影响黑色素瘤的进展。在这里，我们解决了这个问题，并表明与野生型小鼠相比，在类胰蛋白酶缺乏症（Mcpt6- ^/）中黑素瘤的生长明显更高。组织化学分析表明，肥大细胞在野生型和Mctp6 ^-/-的肿瘤基质中均很常见小鼠，并且还揭示了它们在肿瘤实质内的存在。共聚焦显微镜分析显示，类胰蛋白酶被肿瘤细胞吸收。此外，类胰蛋白酶的阳性颗粒从肥大细胞中释放出来，并广泛分布在肿瘤组织内，这表明类胰蛋白酶可能会影响肿瘤的微环境。确实，基因表达分析表明，缺少Mcpt6会导致许多基因（包括Cxcl9，Tgtp2和Gbp10）的表达下降，而5p-miR3098的表达却增强了。血清中的Mcpt6 ^-/-的CXCL9水平较低与野生型小鼠相比。为了进一步支持类胰蛋白酶对黑素瘤的功能影响，重组类胰蛋白酶（Mcpt6）被培养的黑素瘤细胞吸收并导致增殖减少。总之，我们的结果表明肥大细胞类胰蛋白酶对黑素瘤生长具有保护作用。