title: Methylation and loss of Secreted Frizzled-Related Protein 3 enhances melanoma cell migration and invasion.
abstract: BACKGROUND
  Wnt signaling is important in development and can also contribute to the initiation and progression of cancer. The Secreted Frizzled Related Proteins (SFRPs) constitute a family of Wnt modulators, crucial for controlling Wnt signaling. Here we investigate the expression and role of SFRP3 in melanoma.
  
  
  RESULTS
  We show that SFRP3 mRNA is down-regulated in malignant melanoma tumors as compared to normal/benign tissue. Furthermore, we found that SFRP3 expression was lost in the malignant melanoma cell lines, A2058, HTB63 and A375, but not in the non-transformed melanocyte cell line, Hermes 3A. Methylated CpG rich areas were detected in the SFRP3 gene in melanoma cell lines and their SFRP3 expression could be restored using the demethylating agent, 5'aza-deoxycytidine. Addition of recombinant SFRP3 to melanoma cells had no effect on viable cell numbers, but decreased cell migration and invasion. Wnt5a signaling has been shown to increase the migration and invasion of malignant melanoma cells, and high expression of Wnt5a in melanoma tumors has been connected to a poor prognosis. We found that recombinant SFRP3 could inhibit Wnt5a signaling, and that it inhibited melanoma cell migration and invasion in a Wnt5a-dependent manner.
  
  
  CONCLUSIONS
  We conclude that SFRP3 functions as a melanoma migration and invasion suppressor by interfering with Wnt5a signaling.
authors.affiliation: Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Elin J
authors.initials: EJ
authors.lastname: Ekström
authors.forename: Victoria
authors.initials: V
authors.lastname: Sherwood
authors.forename: Tommy
authors.initials: T
authors.lastname: Andersson
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D019175:DNA Methylation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D000071818:Wnt-5a Protein; D000099274:Frizzled-Related Proteins
chemical_list: D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D000099274:Frizzled-Related Proteins; C085389:WNT5A protein, human