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UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-beta 1-FAP-alpha
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
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2017 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 117, no 4, 535-544 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2017. Vol. 117, no 4, 535-544 p.
Keyword [en]
FAP-alpha; UV radiation; melanoma; fibroblast; senescence; invasion; cathepsins; TGF-beta 1
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-140050DOI: 10.1038/bjc.2017.182ISI: 000407094100010PubMedID: 28697174OAI: oai:DiVA.org:liu-140050DiVA: diva2:1136611
Note

Funding Agencies|Swedish Research Council; Welander-Finsen Foundation; Ostgotaregionens Cancer Foundation; Swedish Cancer Society; County Council of Ostergotland; Olle Engkvist Foundation

Available from: 2017-08-28 Created: 2017-08-28 Last updated: 2017-10-05

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The full text will be freely available from 2018-01-11 14:09
Available from 2018-01-11 14:09

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Wäster, PetraOrfanidis, KyriakosEriksson, IdaRosdahl, IngerSeifert, OliverÖllinger, Karin
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Division of Cell BiologyFaculty of Medicine and Health SciencesDepartment of Dermatology and VenerologyDepartment of Clinical Pathology and Clinical Genetics
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