Notch-mediated induction of N-cadherin and α 9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells
Masià Fontana, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Almazán-Moga, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Velasco, Pablo (Hospital Universitari Vall d'Hebron)
Reventós, Jaume (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Torán, Núria (Hospital Universitari Vall d'Hebron)
Sánchez de Toledo, Josep (Hospital Universitari Vall d'Hebron)
Roma, Josep (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gallego, Soledad (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data:	2012
Resum:	Rhabdomyosarcoma (RMS) is the commonest type of soft-tissue sarcoma in children. Patients with metastatic RMS continue to have very poor prognosis. Recently, several works have demonstrated a connection between Notch pathway activation and the regulation of cell motility and invasiveness. However, the molecular mechanisms of this possible relationship remain unclear. The Notch pathway was manipulated pharmacologically and genetically. The mRNA changes were analysed by quantitative PCR and protein variations by western blot and immunofluorescence. Finally, the capabilities of RMS cells to adhere, heal a wound and invade were assessed in the presence of neuronal cadherin (N-cadherin)- and α 9-integrin-blocking antibodies. Cells treated with γ -secretase inhibitor showed lower adhesion capability and downregulation of N-cadherin and α 9-integrin. Genetic manipulation of the Notch pathway led to concomitant variations in N-cadherin and α 9-integrin. Treatment with anti-N-cadherin-blocking antibody rendered marked inhibition of cell adhesion and motility, while anti- α 9-integrin-blocking antibody exerted a remarkable effect on cell adhesion and invasiveness. Neuronal cadherin and α 9-integrin are postulated as leading actors in the association between the Notch pathway and promotion of cell adhesion, motility and invasion, pointing to these proteins and the Notch pathway itself as interesting putative targets for new molecular therapies against metastases in RMS.
Ajuts:	Instituto de Salud Carlos III RD06/0020/1021 Instituto de Salud Carlos III PI11/00740
Nota:	Altres ajuts: This work was supported by grants from Institut Català d'Oncologia (ICO), Instituto de Salud Carlos III (RD06/0020/1021 and PI11/00740), Fundació la Marató de TV3, Asociación Española Contra el Cáncer, Fundació SMALL and Fundació A. BOSCH.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Rhabdomyosarcoma ; Notch ; NCAD ; ITGA9 ; Invasion ; Soft-tissue sarcomas
Publicat a:	British journal of cancer, Vol. 107 (09 2012) , p. 1374-1383, ISSN 1532-1827

DOI: 10.1038/bjc.2012.411
PMID: 22976797

10 p, 2.0 MB

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