title: CTGF is overexpressed in malignant melanoma and promotes cell invasion and migration.
abstract: BACKGROUND
  Malignant melanoma cells are known to have altered expression of growth factors compared with normal human melanocytes. These changes most likely favour tumour growth and progression, and influence tumour environment. The induction of transforming growth factor beta1, 2 and 3 as well as BMP4 and BMP7 expression in malignant melanoma has been reported before, whereas the expression of an important modulator of these molecules, connective tissue growth factor (CTGF), has not been investigated in melanomas until now.
  
  
  METHODS
  Expression of CTGF was analysed in melanoma cell lines and tissue samples by qRT-PCR and immunohistochemistry. To determine the regulation of CTGF expression in malignant melanoma, specific siRNA was used. Additionally, migration, invasion and attachment assays were carried out.
  
  
  RESULTS
  We were able to demonstrate that CTGF expression is upregulated in nine melanoma cell lines and in primary and metastatic melanoma in situ. The transcription factor HIF-1α was revealed as a positive regulator for CTGF expression. Melanoma cells, in which CTGF expression is diminished, show a strong reduction of migratory and invasive properties when compared with controls. Further, treatment of normal human epidermal melanocytes with recombinant CTGF leads to an increase of migratory and invasive behaviour of these cells.
  
  
  CONCLUSIONS
  These results suggest that CTGF promotes melanoma cell invasion and migration and, therefore, has an important role in the progression of malignant melanoma.
authors.affiliation: University of Regensburg Medical School, Institute of Pathology, Franz-Josef-Strauss-Allee 11, Regensburg D-93053, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Braig
authors.forename: S
authors.initials: S
authors.lastname: Wallner
authors.forename: B
authors.initials: B
authors.lastname: Junglas
authors.forename: R
authors.initials: R
authors.lastname: Fuchshofer
authors.forename: A-K
authors.initials: AK
authors.lastname: Bosserhoff
mesh_terms: D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism / Q000502:physiology; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000494:pharmacology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C485671:BAMBI protein, human; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; C526317:CCN2 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D055513:Connective Tissue Growth Factor