title: Expression of the soluble vascular endothelial growth factor receptor-1 in cutaneous melanoma: role in tumour progression.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF)-A, placenta growth factor (PlGF) and their corresponding membrane receptors are involved in autocrine and paracrine regulation of melanoma growth and metastasis. Besides the membrane receptors, a soluble form of the VEGF receptor (VEGFR)-1 (sVEGFR-1) has been identified, that behaves both as a decoy receptor, sequestering VEGF-A and PlGF, and as an extracellular matrix (ECM) molecule, promoting endothelial cell adhesion and migration through the interaction with α5β1 integrin.
  
  
  OBJECTIVE
  To analyse whether sVEGFR-1 plays a role during melanoma progression.
  
  
  METHODS
  sVEGFR-1 expression was evaluated in a panel of 36 melanoma cell lines and 11 primary human melanocyte cultures by quantitative real-time polymerase chain reaction analysis and in specimens of primary or metastatic melanoma lesions from 23 patients by immunohistochemical analysis.
  
  
  RESULTS
  sVEGFR-1 expression was highly upregulated in melanoma cell lines with respect to human melanocytes. Interestingly, cell lines obtained from cutaneous metastases showed a significant reduction of sVEGFR-1 expression, as compared with cell lines derived from primary tumours. These results were confirmed by immunohistochemical analysis of sections from primary skin melanomas and the corresponding cutaneous metastases, suggesting that modulation of sVEGFR-1 expression influences ECM invasion by melanoma cells and metastasis localization. Moreover, we provide evidence that adhesion of melanoma cells to sVEGFR-1 is favoured by the activation of a VEGF-A/VEGFR-2 autocrine loop.
  
  
  CONCLUSIONS
  Our data strongly suggest that sVEGFR-1 plays a role in melanoma progression and that low sVEGFR-1/VEGF-A and sVEGFR-1/transmembrane VEGFR-1 ratios might predict a poor outcome in patients with melanoma.
authors.affiliation: Laboratory of Molecular Oncology, Istituto Dermopatico dell'Immacolata-IRCCS, 00167 Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ruffini
authors.forename: C M
authors.initials: CM
authors.lastname: Failla
authors.forename: A
authors.initials: A
authors.lastname: Orecchia
authors.forename: M R
authors.initials: MR
authors.lastname: Bani
authors.forename: A S
authors.initials: AS
authors.lastname: Dorio
authors.forename: C
authors.initials: C
authors.lastname: Fortes
authors.forename: G
authors.initials: G
authors.lastname: Zambruno
authors.forename: G
authors.initials: G
authors.lastname: Graziani
authors.forename: R
authors.initials: R
authors.lastname: Giavazzi
authors.forename: S
authors.initials: S
authors.lastname: D'Atri
authors.forename: P M
authors.initials: PM
authors.lastname: Lacal
mesh_terms: D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000378:metabolism* / Q000556:secondary; D009363:Neoplasm Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000556:secondary; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D040281:Vascular Endothelial Growth Factor Receptor-1