title: Caveolin-1, Caveolin-2 and Cavin-1 are strong predictors of adipogenic differentiation in human tumors and cell lines of liposarcoma.
abstract: Caveolins (Cav-1, -2 and -3) and Cavins (Cavin-1, -2, -3 and -4) are two protein families controlling the biogenesis and function of caveolae, plasma membrane omega-like invaginations representing the primary site of important cellular processes like endocytosis, cholesterol homeostasis and signal transduction. Caveolae are especially abundant in fat tissue, playing a consistent role in a number of processes, such as the insulin-dependent glucose uptake and transmembrane transport of lipids underlying differentiation, maintenance and adaptive hypertrophy of adipocytes. Based on this premise, in this work we have investigated the expression of caveolar protein components in liposarcoma (LPS), an adipocytic soft tissue sarcoma affecting adults categorized in well-differentiated, dedifferentiated, myxoid and pleomorphic histotypes. By performing an extensive microarray data analysis followed by immunohistochemistry on human LPS tumors, we demonstrated that Cav-1, Cav-2 and Cavin-1 always cluster in all the histotypes, reaching the highest expression in well-differentiated LPS, the least aggressive of the malignant forms composed by tumor cells with a morphology resembling mature adipocytes. In vitro experiments carried out using two human LPS cell lines showed that the expression levels of Cav-1, Cav-2 and Cavin-1 proteins were faintly detectable during cell growth, becoming consistently increased during the accumulation of intracellular lipid droplets characterizing the adipogenic differentiation. Moreover, in differentiated LPS cells the three proteins were also found to co-localize and form molecular aggregates at the plasma membrane, as shown via immunofluorescence and immunoprecipitation analysis. Overall, these data indicate that Cav-1, Cav-2 and Cavin-1 may be considered as reliable markers for identification of LPS tumors characterized by consistent adipogenic differentiation.
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Codenotti
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Vezzoli
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Pietro Luigi
authors.initials: PL
authors.lastname: Poliani
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Cominelli
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Bono
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Hadi
authors.initials: H
authors.lastname: Kabbout
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Faggi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Chiarelli
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Colombi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Zanella
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Biasiotto
authors.affiliation: Department of Laboratory Diagnostics, Spedali Civili of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Montanelli
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy; Department of Laboratory Diagnostics, Spedali Civili of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Monti
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. Electronic address: alessandro.fanzani@unibs.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fanzani
mesh_terms: D050156:Adipogenesis; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D051243:Caveolin 2 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D008080:Liposarcoma / Q000235:genetics*
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D051243:Caveolin 2
keywords: Adipocytes; Caveolae; Caveolins; Cavins; Liposarcoma