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UV radiation promot...
UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-beta 1-FAP-alpha
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- Wäster, Petra (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Orfanidis, Kyriakos (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Hudkliniken i Östergötland
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- Eriksson, Ida (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Rosdahl, Inger (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Hudkliniken i Östergötland
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- Seifert, Oliver (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Ryhov Hospital, Sweden
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- Öllinger, Karin (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi och klinisk genetik
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(creator_code:org_t)
- 2017-07-11
- 2017
- English.
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In: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 117:4, s. 535-544
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Abstract
Subject headings
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- Background: Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-alpha is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-alpha is not yet completely revealed. Methods: Expression of FAP-alpha was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs. Cell migration and invasion was studied in relation to cathepsin activity and secretion of transforming growth factor (TGF)-beta 1. Results: Fibroblast activation protein-a expression was induced by UVR in melanocytes of human skin. The FAP-alpha expression was regulated by UVR-induced release of TGF-beta 1 and cathepsin inhibitors prevented such secretion. In melanoma cell culture models and in a xenograft tumour model of zebrafish embryos, FAP-alpha mediated ECM degradation and facilitated tumour cell dissemination. Conclusions: Our results provide evidence for a sequential reaction axis from UVR via cathepsins, TGF-beta 1 and FAP-alpha expression, promoting cancer cell dissemination and melanoma metastatic spread.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- FAP-alpha; UV radiation; melanoma; fibroblast; senescence; invasion; cathepsins; TGF-beta 1
Publication and Content Type
- ref (subject category)
- art (subject category)
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