ADAM10 is upregulated in melanoma metastasis compared with primary melanoma

J Invest Dermatol. 2010 Mar;130(3):763-73. doi: 10.1038/jid.2009.335. Epub 2009 Oct 29.


ADAM10 (a disintegrin and metalloproteinase 10) is involved in the ectodomain shedding of various substrates, including adhesion molecules such as L1 cell adhesion molecule (L1-CAM) and CD44, which are known to have important roles in the development of malignant melanoma. In our study, we characterized the expression of ADAM10 in melanoma cells in vitro and in vivo. Immunohistochemical analysis on tissue microarrays indicated that ADAM10 expression was significantly elevated in melanoma metastasis compared with primary melanomas. In vitro downregulation of ADAM10 with specific small interfering RNA (siRNA) resulted in a suppression of the anchorage-independent cell growth and reduced the migration of melanoma cells. In addition, overexpression of ADAM10 induced the migration of melanoma cells. In cell lines from melanoma patients with metastasis, ADAM10 was significantly overexpressed, and ADAM10 expression correlated with increased cell proliferation. Furthermore, we present evidence that ADAM10 is involved in the release of L1-CAM from melanoma cells. It is important that knockdown of cellular L1-CAM reduced the migration of melanoma cells and abrogated the chemoresistance against cisplatin. In contrast, soluble L1-CAM had no effect on melanoma cell migration or cell survival. Taken together, our data demonstrate that ADAM10 and L1-CAM have important roles during melanoma progression and both molecules represent attractive targets for therapeutical intervention of melanomas.

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism*
  • ADAM10 Protein
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism*
  • Antineoplastic Agents / pharmacology
  • Cell Division / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cisplatin / pharmacology
  • Disease Progression
  • Drug Resistance, Neoplasm / physiology
  • Endothelial Cells / cytology
  • Epidermis / metabolism
  • Epidermis / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Melanoma / drug therapy
  • Melanoma / physiopathology*
  • Melanoma / secondary*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neural Cell Adhesion Molecule L1 / genetics
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Nevus, Pigmented / pathology
  • Nevus, Pigmented / physiopathology
  • RNA, Small Interfering
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / physiopathology*
  • Umbilical Veins / cytology
  • Up-Regulation / physiology


  • Antineoplastic Agents
  • Membrane Proteins
  • Neural Cell Adhesion Molecule L1
  • RNA, Small Interfering
  • Amyloid Precursor Protein Secretases
  • ADAM Proteins
  • ADAM10 Protein
  • ADAM10 protein, human
  • Cisplatin