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


Antsiferova, M; Huber, M; Meyer, Michael; Piwko-Czuchra, A; Ramadan, T; MacLeod, A S; Havran, W L; Dummer, R; Hohl, D; Werner, S (2011). Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response. Nature Communications, 2:576.

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.

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.

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18 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:December 2011
Deposited On:02 Feb 2012 20:13
Last Modified:05 Apr 2016 15:31
Publisher:Nature Publishing Group
ISSN:2041-1723 (E)
Publisher DOI:https://doi.org/10.1038/ncomms1585
PubMed ID:22146395

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