Insulin-Like-Growth-Factor-Binding-Protein-3 IGFBP-3 Contrasts Melanoma Progression In Vitro and In VivoReportar como inadecuado

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Insulin-like-factor-binding-protein 3 IGFBP-3 is known to modulate the activity of insulin-like growth factors IGFs besides having a number of IGF-independent effects on cell growth and survival. IGFBP-3 has been reported to decrease significantly in the blood serum of patients affected by certain cancers. In the present work, we have evaluated the levels of IGFBP-3 in the blood serum and tissues of patients affected by cutaneous melanoma, showing that loss of IGFBP-3 from both is strongly correlated with disease progression and reduced survival. In vitro treatment with IGFBP-3 of human and murine metastatic melanoma cell lines specifically inhibited the cells- migratory and invasive behaviour, inducing up-regulation of melanocytic differentiation markers such as tyrosinase activity and melanin content. A molecular analysis of the cellular pathways transducing the effect of IGFBP-3 implicated the Akt-GSK3β axis. Moreover, administration of IGFBP-3 in vivo to SCID mice inoculated with human metastatic melanoma cells strongly reduced or completely inhibited tumor growth. In summary, IGFBP-3 appears to exert a specific inhibitory effect on melanoma growth and dissemination, suggesting that it may qualify as a useful therapeutic agent in melanomas and perhaps other cancers, at the least as a valid adjuvant therapy during treatment with conventional anti-tumoral drugs.

Autor: Antimo Naspi , Vincenzo Panasiti , Franco Abbate, Vincenzo Roberti, Valeria Devirgiliis, Michela Curzio, Martina Borghi, Francesc



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