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 upregulation 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. © 2014 Naspi et al.

Insulin-like-growth-factor-binding-protein-3 (IGFBP-3) contrasts melanoma progression in vitro and in vivo / Naspi, Antimo; Panasiti, Vincenzo; Abbate, Franco; Roberti, Vincenzo; Devirgiliis, Valeria; Curzio, Michela; Martina, Borghi; Francesco, Lozupone; Simone, Carotti; Sergio, Morini; Gaudio, Eugenio; Calvieri, Stefano; Londei, Paola. - In: PLOS ONE. - ISSN 1932-6203. - 9:6(2014), p. e98641. [10.1371/journal.pone.0098641]

Insulin-like-growth-factor-binding-protein-3 (IGFBP-3) contrasts melanoma progression in vitro and in vivo

NASPI, ANTIMO;PANASITI, VINCENZO;ABBATE, Franco;ROBERTI, VINCENZO;DEVIRGILIIS, VALERIA;CURZIO, MICHELA;GAUDIO, EUGENIO;CALVIERI, Stefano;LONDEI, Paola
2014

Abstract

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 upregulation 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. © 2014 Naspi et al.
2014
01 Pubblicazione su rivista::01a Articolo in rivista
Insulin-like-growth-factor-binding-protein-3 (IGFBP-3) contrasts melanoma progression in vitro and in vivo / Naspi, Antimo; Panasiti, Vincenzo; Abbate, Franco; Roberti, Vincenzo; Devirgiliis, Valeria; Curzio, Michela; Martina, Borghi; Francesco, Lozupone; Simone, Carotti; Sergio, Morini; Gaudio, Eugenio; Calvieri, Stefano; Londei, Paola. - In: PLOS ONE. - ISSN 1932-6203. - 9:6(2014), p. e98641. [10.1371/journal.pone.0098641]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/571171
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 16
social impact