Dickkopf-1 inhibits the invasive activity of melanoma cells

Clin Exp Dermatol. 2012 Jun;37(4):404-10. doi: 10.1111/j.1365-2230.2011.04276.x. Epub 2012 Mar 15.

Abstract

Background: Malignant melanoma (MM) has the highest morbidity of any malignant tumour. It is known that the Wnt pathway of enhances the development of melanoma. Dickkopf (DKK)-1, an inhibitor of the canonical Wnt/β-catenin pathway, might also inhibit the development of MM.

Aim: To examine the influence of DKK-1 expression on the invasive activity of MM cells.

Methods: To detect DKK-1 expression level we performed immunohistochemistry on human tissue sections of normal skin, malignant melanoma (MM) in situ, and MM with lymph-node metastasis. To clarify the role that DDK-1 plays in the invasive activity of MM cells, we performed a scratch-wound healing assay and Transwell invasion assay for A375 cells infected with appropriate recombinant adenoviruses, then assessed the migration of these cells.

Results: Fewer DDK1-overexpressing A375 cells than control cells migrated to the scratch-wound area or through the pores of the Transwell membrane to the lower wells. Downregulation of DKK-1 in A375 cells had the opposite effect.

Conclusions: In the present study, we found for the first time that DKK-1 expression inhibits the invasive activity of MM cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Neoplasm Invasiveness
  • Skin / metabolism
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Wound Healing

Substances

  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins