1. Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response.
- Author
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Antsiferova M, Huber M, Meyer M, Piwko-Czuchra A, Ramadan T, MacLeod AS, Havran WL, Dummer R, Hohl D, and Werner S
- Subjects
- Animals, Carcinoma, Squamous Cell immunology, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Cell Differentiation genetics, Cell Line, Cell Proliferation, Cell Transformation, Neoplastic immunology, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Epidermis immunology, Epidermis pathology, Humans, Keratinocytes immunology, Keratinocytes metabolism, Langerhans Cells immunology, Langerhans Cells metabolism, Mice, Mice, Transgenic, Reverse Transcriptase Polymerase Chain Reaction, Skin Neoplasms immunology, Skin Neoplasms metabolism, Skin Neoplasms pathology, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Wound Healing physiology, Activins genetics, Activins immunology, Activins metabolism, Carcinoma, Squamous Cell genetics, Cell Transformation, Neoplastic genetics, Epidermis metabolism, Gene Expression Regulation, Neoplastic, Skin Neoplasms genetics
- Abstract
Activin is an important orchestrator of wound repair, but its potential role in skin carcinogenesis has not been addressed. Here we show using different types of genetically modified mice that enhanced levels of activin in the skin promote skin tumour formation and their malignant progression through induction of a pro-tumourigenic microenvironment. This includes accumulation of tumour-promoting Langerhans cells and regulatory T cells in the epidermis. Furthermore, activin inhibits proliferation of tumour-suppressive epidermal γδ T cells, resulting in their progressive loss during tumour promotion. An increase in activin expression was also found in human cutaneous basal and squamous cell carcinomas when compared with control tissue. These findings highlight the parallels between wound healing and cancer, and suggest inhibition of activin action as a promising strategy for the treatment of cancers overexpressing this factor.
- Published
- 2011
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