Paired Basic Amino Acid-cleaving Enzyme 4 (PCSK6): An Emerging New Target Molecule in Human Melanoma

Although recent therapeutic developments raise hope, melanoma remains a devastating disease with a need for new treatment targets. In other tumours prohormone convertases have been shown to be pro-tumourigenic as they are involved in processing preforms of matrix-metalloproteinases, growth factors a...

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Bibliographic Details
Published in:Acta dermato-venereologica 2020-05, Vol.100 (10), p.adv00157
Main Authors: Weishaupt, Carsten, Mastrofrancesco, Arianna, Metze, Dieter, Kemper, Björn, Stegemann, Agatha, Picardo, Mauro, Klein-Szanto, Andres J P, Böhm, Markus
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - therapeutic use
Cell Line, Tumor
Cell Movement
Cell Proliferation
Gene Expression Regulation, Neoplastic
Humans
Investigative Report
Melanoma - drug therapy
Melanoma - enzymology
Melanoma - genetics
Melanoma - pathology
Mice, Hairless
Mice, SCID
Molecular Targeted Therapy
Neoplasm Invasiveness
Proprotein Convertases - antagonists & inhibitors
Proprotein Convertases - genetics
Proprotein Convertases - metabolism
Serine Endopeptidases - genetics
Serine Endopeptidases - metabolism
Serine Proteinase Inhibitors - therapeutic use
Signal Transduction
Skin Neoplasms - drug therapy
Skin Neoplasms - enzymology
Skin Neoplasms - genetics
Skin Neoplasms - pathology
Tumor Burden
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Summary:Although recent therapeutic developments raise hope, melanoma remains a devastating disease with a need for new treatment targets. In other tumours prohormone convertases have been shown to be pro-tumourigenic as they are involved in processing preforms of matrix-metalloproteinases, growth factors and adhesion molecules. The aim of this study was to look for new treatment options for melanoma, by investigating the role of the prohormone convertase Paired basic Amino acid-Cleaving Enzyme 4 (PACE4/PCSK6) in melanoma cell lines and human melanoma tissue. PACE4-transfected A375 melanoma cells displayed significantly increased proliferation, MMP-2 production, gelatinase activity and migratory capacity in vitro compared with sham-transfected cells. In vivo, elevated PACE4 expression resulted in significantly increased tumour growth on immunodeficient mice. In the majority of 45 human primary melanomas and melanoma metastases ex vivo PACE4 immunoreactivity was detectable, while it was absent in in situ melanomas. These results indicate PACE4 as a regulator of melanoma cell aggressiveness.
ISSN:1651-2057
0001-5555
1651-2057
DOI:10.2340/00015555-3525