title: 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.affiliation: Department of Biology, Institute of Cell Biology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Antsiferova
authors.forename: Marcel
authors.initials: M
authors.lastname: Huber
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Piwko-Czuchra
authors.forename: Tamara
authors.initials: T
authors.lastname: Ramadan
authors.forename: Amanda S
authors.initials: AS
authors.lastname: MacLeod
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Havran
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
authors.forename: Sabine
authors.initials: S
authors.lastname: Werner
mesh_terms: D028341:Activins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D028341:Activins