title: The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling.
abstract: 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.
authors: IFOM - The FIRC Institute of Molecular Oncology, Milano, Italy.
authors: Silvia
authors: S
authors: Zecchini
authors: Lorenzo
authors: L
authors: Bombardelli
authors: Alessandra
authors: A
authors: Decio
authors: Marco
authors: M
authors: Bianchi
authors: Giovanni
authors: G
authors: Mazzarol
authors: Fabio
authors: F
authors: Sanguineti
authors: Giovanni
authors: G
authors: Aletti
authors: Luigi
authors: L
authors: Maddaluno
authors: Vladimir
authors: V
authors: Berezin
authors: Elisabeth
authors: E
authors: Bock
authors: Chiara
authors: C
authors: Casadio
authors: Giuseppe
authors: G
authors: Viale
authors: Nicoletta
authors: N
authors: Colombo
authors: Raffaella
authors: R
authors: Giavazzi
authors: Ugo
authors: U
authors: Cavallaro
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000473:pathology* / Q000556:secondary; D002465:Cell Movement; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000556:secondary; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019006:Neural Cell Adhesion Molecules; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1