title: Melanoma growth and progression after ultraviolet a irradiation: impact of lysosomal exocytosis and cathepsin proteases.
abstract: Ultraviolet (UV) irradiation is a risk factor for development of malignant melanoma. UVA-induced lysosomal exocytosis and subsequent cell growth enhancement was studied in malignant melanoma cell lines and human skin melanocytes. UVA irradiation caused plasma membrane damage that was rapidly repaired by calcium-dependent lysosomal exocytosis. Lysosomal content was released into the culture medium directly after irradiation and such conditioned media stimulated the growth of non-irradiated cell cultures. By comparing melanocytes and melanoma cells, it was found that only the melanoma cells spontaneously secreted cathepsins into the surrounding medium. Melanoma cells from a primary tumour showed pronounced invasion ability, which was prevented by addition of inhibitors of cathepsins B, D and L. Proliferation was reduced by cathepsin L inhibition in all melanoma cell lines, but did not affect melano-cyte growth. In conclusion, UVA-induced release of cathepsins outside cells may be an important factor that promotes melanoma growth and progression.
authors: Division of Dermatology and Venereology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors: Cecilia Bivik
authors: CB
authors: Eding
authors: Jakob
authors: J
authors: Domert
authors: Petra
authors: P
authors: Wäster
authors: Fredrik
authors: F
authors: Jerhammar
authors: Inger
authors: I
authors: Rosdahl
authors: Karin
authors: K
authors: Öllinger
mesh_terms: D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D018450:Disease Progression; D005089:Exocytosis / Q000528:radiation effects*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology* / Q000528:radiation effects*; D008544:Melanocytes / Q000201:enzymology / Q000528:radiation effects; D008545:Melanoma / Q000201:enzymology* / Q000556:secondary; D009361:Neoplasm Invasiveness; D011480:Protease Inhibitors / Q000494:pharmacology; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D011480:Protease Inhibitors; D002403:Cathepsins