ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

• Published in: Biochemical and biophysical research communications Vol. 401; no. 3; pp. 363 - 369
• Main Authors: Ungerer, Christopher, Doberstein, Kai, Bürger, Claudia, Hardt, Katja, Boehncke, Wolf-Henning, Böhm, Beate, Pfeilschifter, Josef, Dummer, Reinhard, Mihic-Probst, Daniela, Gutwein, Paul
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.10.2010
• Subjects: 60 APPLIED LIFE SCIENCES; ADAM Proteins - antagonists & inhibitors; ADAM Proteins - biosynthesis; ADAM Proteins - genetics; ADAM15; ANIMAL CELLS; ANIMAL TISSUES; Animals; Cell Adhesion; Cell Line, Tumor; Cell Movement; CELL PROLIFERATION; Humans; Invasion; LUNGS; Malignant melanoma; MELANIN; Melanoma - enzymology; Melanoma - pathology; MELANOMAS; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; METASTASES; MICE; Neoplasm Metastasis; PATIENTS; Proliferation; PROTEINS; Skin Neoplasms - enzymology; Skin Neoplasms - pathology; Tumor Suppressor Proteins - antagonists & inhibitors; Tumor Suppressor Proteins - biosynthesis; Tumor Suppressor Proteins - genetics; Proliferation; ADAM15; Invasion; Malignant melanoma
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2010.09.055

► Strong ADAM15 expression is found in normal melanocytes. ► ADAM15 expression is significantly downregulated in patients with melanoma metastasis. ► TGF-β can downregulate ADAM15 expression in melanoma cells. ► Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. ► Conclusion: ADAM15 represents an tumor suppressor protein in 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.