title: Caveolin 1 is a marker of poor differentiation in Rhabdomyosarcoma.
abstract: Caveolins consist of three different membrane scaffolding proteins that play a variety of processes in different tissues. In skeletal muscle caveolins are differentially distributed, with Caveolin 1 (Cav-1) being uniquely expressed in satellite cells and Caveolin 3 (Cav-3) in mature myofibers. Rhabdomyosarcoma (RMS) represents the most common childhood soft-tissue sarcoma arising from mesenchimal precursors which fail to undergo proper commitment to muscle lineage. Cav-3 has been proposed as a marker of RMS with a high degree of differentiation, while biological significance of Cav-1 expression in RMS is still a matter of debate. In the present study we show that Cav-1 is predominantly expressed in the embryonal RMS histotype, as further confirmed by transcript and protein analysis in different in vitro human RMS cell lines. Immature cell phenotype of human embryonal RD line, carrying spontaneous activating RAS mutations, was significantly associated to ERK MAPK signalling pathway and featured by high Cav-1 levels, whereas pharmacological attenuation of the ERK pathway, improving cell differentiation, lead to Cav-1 down-regulation. Overall, these data place Cav-1 as a valuable marker of diagnosis for RMS characterised by low degree of differentiation.
authors.affiliation: Department of Biomedical Sciences and Biotechnologies and Interuniversity Institute of Myology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Rossi
authors.forename: Pietro Luigi
authors.initials: PL
authors.lastname: Poliani
authors.forename: Manuela
authors.initials: M
authors.lastname: Cominelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Bozzato
authors.forename: Raffaella
authors.initials: R
authors.lastname: Vescovi
authors.forename: Eugenio
authors.initials: E
authors.lastname: Monti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fanzani
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018482:Muscle, Skeletal / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018233:Rhabdomyosarcoma, Embryonal / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D051242:Caveolin 1; D048049:Extracellular Signal-Regulated MAP Kinases