Differential inhibition of the TGF-b signaling pathway in HCC cells using the small molecule inhibitor LY2157299 and the D10 monoclonal antibody against TGF-β receptor Type II

We investigated blocking the TGF-b signaling pathway in HCC using two small molecule inhibitors (LY2157299, LY2109761) and a neutralizing humanized antibody (D10) against TGF-bRII. LY2157299 and LY2109761 inhibited HCC cell migration on Laminin-5, Fibronectin, Vitronectin, Fibrinogen and Collagen-I...

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Detalles Bibliográficos
Autores: Dituri, Francesco, Mazzocca, Antonio, Peidrò, Fernando Juan, Papappicco, Patrizia, Fabregat Romero, Isabel, De Santis, Flavia, Paradiso, Angelo, Sabbà, Carlo, Giannelli, Gianluigi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/97493
Acceso en línea:https://hdl.handle.net/2445/97493
Access Level:acceso abierto
Palabra clave:Anticossos monoclonals
Fosforilació
Càncer de fetge
Factors de creixement
Monoclonal antibodies
Phosphorylation
Liver cancer
Growth factors
Descripción
Sumario:We investigated blocking the TGF-b signaling pathway in HCC using two small molecule inhibitors (LY2157299, LY2109761) and a neutralizing humanized antibody (D10) against TGF-bRII. LY2157299 and LY2109761 inhibited HCC cell migration on Laminin-5, Fibronectin, Vitronectin, Fibrinogen and Collagen-I and de novo phosphorylation of pSMAD2. LY2157299 inhibited HCC migration and cell growth independently of the expression levels of TGF-bRII. In contrast to LY2157299, D10 showed a reduction in pSMAD2 only after a short exposure. This study supports the use of LY2157299 in clinical trials, and presents new insights into TGF-b receptor cycling in cancer cells.

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