The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

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

doi:10.1002/emmm.201100152

The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

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

Institut for Neurovidenskab

46 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	EMBO Molecular Medicine
Vol/bind	3
Udgave nummer	8
Sider (fra-til)	480-494
Antal sider	15
DOI	https://doi.org/10.1002/emmm.201100152
Status	Udgivet - aug. 2011

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10.1002/emmm.201100152

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Zecchini, S., Bombardelli, L., Decio, A., Bianchi, M., Mazzarol, G., Sanguineti, F., Aletti, G., Maddaluno, L., Berezin, V., Bock, E., Casadio, C., Viale, G., Colombo, N., Giavazzi, R., & Cavallaro, U. (2011). The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling. EMBO Molecular Medicine, 3(8), 480-494. https://doi.org/10.1002/emmm.201100152

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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.",

keywords = "Animals, Carcinoma, Cell Movement, Disease Models, Animal, Female, Humans, Immunohistochemistry, Mice, Neoplasm Invasiveness, Neoplasm Metastasis, Neural Cell Adhesion Molecules, Ovarian Neoplasms, Receptor, Fibroblast Growth Factor, Type 1, Signal Transduction",

author = "Silvia Zecchini and Lorenzo Bombardelli and Alessandra Decio and Marco Bianchi and Giovanni Mazzarol and Fabio Sanguineti and Giovanni Aletti and Luigi Maddaluno and Vladimir Berezin and Elisabeth Bock and Chiara Casadio and Giuseppe Viale and Nicoletta Colombo and Raffaella Giavazzi and Ugo Cavallaro",

note = "Copyright {\textcopyright} 2011 EMBO Molecular Medicine.",

year = "2011",

month = aug,

doi = "10.1002/emmm.201100152",

language = "English",

volume = "3",

pages = "480--494",

journal = "EMBO Molecular Medicine",

issn = "1757-4676",

publisher = "Wiley-Blackwell",

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TY - JOUR

T1 - The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

AU - Zecchini, Silvia

AU - Bombardelli, Lorenzo

AU - Decio, Alessandra

AU - Bianchi, Marco

AU - Mazzarol, Giovanni

AU - Sanguineti, Fabio

AU - Aletti, Giovanni

AU - Maddaluno, Luigi

AU - Berezin, Vladimir

AU - Bock, Elisabeth

AU - Casadio, Chiara

AU - Viale, Giuseppe

AU - Colombo, Nicoletta

AU - Giavazzi, Raffaella

AU - Cavallaro, Ugo

PY - 2011/8

Y1 - 2011/8

N2 - 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.

AB - 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.

KW - Animals

KW - Carcinoma

KW - Cell Movement

KW - Disease Models, Animal

KW - Female

KW - Humans

KW - Immunohistochemistry

KW - Mice

KW - Neoplasm Invasiveness

KW - Neoplasm Metastasis

KW - Neural Cell Adhesion Molecules

KW - Ovarian Neoplasms

KW - Receptor, Fibroblast Growth Factor, Type 1

KW - Signal Transduction

U2 - 10.1002/emmm.201100152

DO - 10.1002/emmm.201100152

M3 - Journal article

C2 - 21739604

SN - 1757-4676

VL - 3

SP - 480

EP - 494

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

IS - 8

ER -

The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

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