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The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Silvia Zecchini
  • Lorenzo Bombardelli
  • Alessandra Decio
  • Marco Bianchi
  • Giovanni Mazzarol
  • Fabio Sanguineti
  • Giovanni Aletti
  • Luigi Maddaluno
  • Vladimir Berezin
  • Elisabeth Bock
  • Chiara Casadio
  • Giuseppe Viale
  • Nicoletta Colombo
  • Raffaella Giavazzi
  • Ugo Cavallaro
Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm, which mainly disseminates to organs of the peritoneal cavity, an event mediated by molecular mechanisms that remain elusive. Here, we investigated the expression and functional role of neural cell adhesion molecule (NCAM), a cell surface glycoprotein involved in brain development and plasticity, in EOC. NCAM is absent from normal ovarian epithelium but becomes highly expressed in a subset of human EOC, in which NCAM expression is associated with high tumour grade, suggesting a causal role in cancer aggressiveness. We demonstrate that NCAM stimulates EOC cell migration and invasion in vitro and promotes metastatic dissemination in mice. This pro-malignant function of NCAM is mediated by its interaction with fibroblast growth factor receptor (FGFR). Indeed, not only FGFR signalling is required for NCAM-induced EOC cell motility, but targeting the NCAM/FGFR interplay with a monoclonal antibody abolishes the metastatic dissemination of EOC in mice. Our results point to NCAM-mediated stimulation of FGFR as a novel mechanism underlying EOC malignancy and indicate that this interplay may represent a valuable therapeutic target.
OriginalsprogEngelsk
TidsskriftEMBO Molecular Medicine
Vol/bind3
Udgave nummer8
Sider (fra-til)480-494
Antal sider15
DOI
StatusUdgivet - 2011

ID: 40354792