Mast cells protect from skin tumor development and limit tumor growth during cutaneous de novo carcinogenesis in a Kit-dependent mouse model.
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.
Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Frank
F
Siebenhaar
Martin
M
Metz
Marcus
M
Maurer
D015127:9,10-Dimethyl-1,2-benzanthracene; D019264:Adoptive Transfer; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002452:Cell Count; D015550:Cell Degranulation; D019610:Cytoprotection; D004195:Disease Models, Animal; D005260:Female; D006098:Granulocytes; D008264:Macrophages; D008407:Mast Cells / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate; D047368:Tumor Burden / Q000235:genetics
D015127:9,10-Dimethyl-1,2-benzanthracene; D019009:Proto-Oncogene Proteins c-kit; D013755:Tetradecanoylphorbol Acetate
carcinogenesis; inflammation; mast cells