ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma.
In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-β downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.
Ungerer
Christopher
C
Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main, Germany.
Doberstein
Kai
K
Bürger
Claudia
C
Hardt
Katja
K
Boehncke
Wolf-Henning
WH
Böhm
Beate
B
Pfeilschifter
Josef
J
Dummer
Reinhard
R
Mihic-Probst
Daniela
D
Gutwein
Paul
P
D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; D051722:ADAM Proteins; C098660:ADAM15 protein, human