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UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-beta 1-FAP-alpha
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
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2017 (engelsk)Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 117, nr 4, s. 535-544Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
NATURE PUBLISHING GROUP , 2017. Vol. 117, nr 4, s. 535-544
Emneord [en]
FAP-alpha; UV radiation; melanoma; fibroblast; senescence; invasion; cathepsins; TGF-beta 1
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Identifikatorer
URN: urn:nbn:se:liu:diva-140050DOI: 10.1038/bjc.2017.182ISI: 000407094100010PubMedID: 28697174OAI: oai:DiVA.org:liu-140050DiVA, id: diva2:1136611
Merknad

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

Tilgjengelig fra: 2017-08-28 Laget: 2017-08-28 Sist oppdatert: 2017-10-05

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