UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-ß1-FAP-α.
Br J Cancer
; 117(4): 535-544, 2017 Aug 08.
Article
in En
| MEDLINE
| ID: mdl-28697174
ABSTRACT
BACKGROUND:
Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-α 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-α is not yet completely revealed.METHODS:
Expression of FAP-α 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)-ß1.RESULTS:
Fibroblast activation protein-α expression was induced by UVR in melanocytes of human skin. The FAP-α expression was regulated by UVR-induced release of TGF-ß1 and cathepsin inhibitors prevented such secretion. In melanoma cell culture models and in a xenograft tumour model of zebrafish embryos, FAP-α mediated ECM degradation and facilitated tumour cell dissemination.CONCLUSIONS:
Our results provide evidence for a sequential reaction axis from UVR via cathepsins, TGF-ß1 and FAP-α expression, promoting cancer cell dissemination and melanoma metastatic spread.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin Neoplasms
/
Ultraviolet Rays
/
Serine Endopeptidases
/
Cathepsins
/
Transforming Growth Factor beta
/
Gelatinases
/
Melanoma
/
Membrane Proteins
/
Nevus
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Br J Cancer
Year:
2017
Document type:
Article
Affiliation country:
Suecia