Abstract 3827: Caveolin-1 acts as a tumor suppressor promoting muscular differentiation in alveolar rhabdomyosarcomas.

Abstract

Abstract Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with a histological variant of rhabdomyosarcoma known as alveolar rhabdomyosarcoma (ARMS) have a 5-year survival of <30%. Caveolin-1 (CAV-1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signaling. We report that CAV1 is expressed in embryonic rhabdomyosarcoma (ERMS) cell lines and tumor samples. However, in 3 out of 4 different ARMS cell lines and 8 out of 9 clinical samples CAV1 expression is either undetectable or very low. The epigenetic silencing of CAV1 by hypermethylation was tested in ARMS cells before and after azacytidine treatment. CAV1 methylation was evaluated by bisulfite genomic sequencing. Re-expression of CAV1 in two of these cell lines is cytostatic and promotes differentiation. In vivo, CAV1-expressing tumor cells showed growth delay and features of muscular differentiation in comparison with untransfected and vector transfected cells. Our results demonstrated that CAV1 could function as a potent tumor suppressor in ARMS tumors. Inhibition of CAV1 function could contribute to aberrant cell proliferation, leading to ARMS development. The use of peptides that mimic CAV1 function may be of therapeutic use for the treatment of ARMS. Citation Format: Juan Huertas-Martinez, Ignasi Barrau, Miguel Sáinz-Jaspeado, Laura Lagares-Tena, Silvia Mateo-Lozano, Jaume Mora, Josep Roma, Soledad Gallego, Sebastian Moran, Manel Esteller, Xavier Garcia del Muro, Oscar M. Tirado. Caveolin-1 acts as a tumor suppressor promoting muscular differentiation in alveolar rhabdomyosarcomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3827. doi:10.1158/1538-7445.AM2013-3827