Mast cells protect from skin tumor development and limit tumor growth during cutaneous de novo carcinogenesis in a Kit-dependent mouse model

作者：Siebenhaar Frank^*; Metz Martin; Maurer Marcus

来源：Experimental Dermatology, 2014, 23(3): 159-164.

DOI：10.1111/exd.12328

• carcinogenesis
• inflammation
• mast cells

Epidermal tumors belong to the most frequent type of neoplasms, and tumor-associated accumulation of mast cells (MCs) has first been observed more than a century ago. Therefore, MCs have been implicated in tumor development and growth; however, the results regarding the role of MC in cutaneous de novo carcinogenesis are still controversially discussed. Here, we subjected MC-deficient Kit(W)/Kit(W-v) mice to chemical skin carcinogenesis. Tumors were induced using the carcinogen 7,12-dimethylbenz[a]-anthracene and subsequent treatment with the tumor promoter 12-tetradecanoyl-phorbol-13-acetat. The treatment resulted in pronounced inflammatory cell infiltrates that were diminished in MC-deficient animals. Unexpectedly, tumor development and growth was significantly increased in MC-deficient Kit(W)/Kit(W-v) mice. The repair of their MC deficiency by local adoptive transfer of MCs normalized tumor incidence and growth. The recruitment of skin-infiltrating immune cells, particularly of F4/80+ monocytes, Gr-1+ granulocytes, B220+ B cells and CD8+ T lymphocytes, to sites of tumor development was, in part, also controlled by MCs. Recent evidence indicated the importance of local antitumor tissue immunity which prevents tumor development. These findings suggest a critical role for MCs in mediating these host antitumor immune responses in the skin.

• 出版日期2014-3