TY - JOUR
T1 - Paired basic amino acid-cleaving enzyme 4 (PCSK6)
T2 - An emerging new target molecule in human melanoma
AU - Weishaupt, Carsten
AU - Mastrofrancesco, Arianna
AU - Metze, Dieter
AU - Kemper, Björn
AU - Stegemann, Agatha
AU - Picardo, Mauro
AU - Klein-Szanto, Andres J.P.
AU - Böhm, Markus
N1 - Funding Information:
The authors thank Gert von Bally for scientific support, Ilka Wolff, Britta Ringelkamp, Andrea Wissel, Angelika Vollmer and Steffi Ketelhut for expert technical assistance. The work was supported by the Innovative Medizinische Forschung of the University of Münster (grant number: WE110817) to CW and MB and by the Germany Federal Ministry for Education and Research to BK and GvB (grant number: FKZ 13N10937).
Publisher Copyright:
© 2020 Acta Dermato-Venereologica.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5
Y1 - 2020/5
N2 - 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 45ctaDV 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.
AB - 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 45ctaDV 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.
KW - Carcinogenesis
KW - Melanocytes
KW - Melanoma
KW - PACE4
KW - PCSK6
KW - Prohormone convertases
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U2 - 10.2340/00015555-3525
DO - 10.2340/00015555-3525
M3 - Article
C2 - 32449780
AN - SCOPUS:85086482038
VL - 100
SP - 1
EP - 9
JO - Acta Dermato-Venereologica
JF - Acta Dermato-Venereologica
SN - 0001-5555
IS - 10
M1 - adv00157
ER -