Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response.

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.

• Authors: Maria Antsiferova, Marcel Huber, Michael Meyer, Aleksandra Piwko-Czuchra, Tamara Ramadan, Amanda S MacLeod, Wendy L Havran, Reinhard Dummer, Daniel Hohl, Sabine Werner
• Journal: Nature communications (Nat Commun) Vol. 2 Pg. 576 (Dec 06 2011) ISSN: 2041-1723 [Electronic] England
• PMID: 22146395 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Activins

Topics

• Activins (genetics, immunology, metabolism)
• Animals
• Carcinoma, Squamous Cell (genetics, immunology, metabolism, pathology)
• Cell Differentiation (genetics)
• Cell Line
• Cell Proliferation
• Cell Transformation, Neoplastic (genetics, immunology, metabolism, pathology)
• Epidermis (immunology, metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Keratinocytes (immunology, metabolism)
• Langerhans Cells (immunology, metabolism)
• Mice
• Mice, Transgenic
• Reverse Transcriptase Polymerase Chain Reaction
• Skin Neoplasms (genetics, immunology, metabolism, pathology)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Wound Healing (physiology)