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

Naspi A, Panasiti V, Abbate F, Roberti V, Devirgiliis V, Curzio M, Borghi M, Lozupone F, Carotti S, Morini S, Gaudio E, Calvieri S, Londei P - PLoS ONE (2014)

Bottom Line: 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.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 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.

View Article: PubMed Central - PubMed

Affiliation: Istituto Pasteur-Fondazione Cenci-Bolognetti, Dpt. Biotecnologie Cellulari ed Ematologia, University of Rome Sapienza, Rome, Italy.

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 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.

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Inverse correlation between immuno-histochemical expression of IGFBP-3 and MMP-9.Comparison of the immunohistochemistry for IGFBP-3 (A, C, E) and MMP-9 (B, D, F) in sequential sections obtained from primary melanomas and dermal metastases. The asterisks mark the melanocytes nests while the arrows indicate the stromal tissue. Original magnification X100. The IGFBP-3 and MMP-9 reactive cells were counted, and the scores determined, as described in Fig. 1 and in the Methods section.
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pone-0098641-g003: Inverse correlation between immuno-histochemical expression of IGFBP-3 and MMP-9.Comparison of the immunohistochemistry for IGFBP-3 (A, C, E) and MMP-9 (B, D, F) in sequential sections obtained from primary melanomas and dermal metastases. The asterisks mark the melanocytes nests while the arrows indicate the stromal tissue. Original magnification X100. The IGFBP-3 and MMP-9 reactive cells were counted, and the scores determined, as described in Fig. 1 and in the Methods section.

Mentions: Secondly, tumour samples taken from patients were immuno-stained for both IGFBP-3 and MMP-9. As shown in Fig. 2 (C,D,E), the MMP-9 immunoreactivity of both tumor and stromal cells was significantly higher in metastatic lesions than in primary tumors. Strikingly, there was an almost perfect inverse correlation between the areas of low or no IGFBP-3 staining and those of high MMP-9 staining (Fig. 3), suggesting that the enzyme could indeed have a role in the degradation of IGFBP-3.


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

Naspi A, Panasiti V, Abbate F, Roberti V, Devirgiliis V, Curzio M, Borghi M, Lozupone F, Carotti S, Morini S, Gaudio E, Calvieri S, Londei P - PLoS ONE (2014)

Inverse correlation between immuno-histochemical expression of IGFBP-3 and MMP-9.Comparison of the immunohistochemistry for IGFBP-3 (A, C, E) and MMP-9 (B, D, F) in sequential sections obtained from primary melanomas and dermal metastases. The asterisks mark the melanocytes nests while the arrows indicate the stromal tissue. Original magnification X100. The IGFBP-3 and MMP-9 reactive cells were counted, and the scores determined, as described in Fig. 1 and in the Methods section.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048209&req=5

pone-0098641-g003: Inverse correlation between immuno-histochemical expression of IGFBP-3 and MMP-9.Comparison of the immunohistochemistry for IGFBP-3 (A, C, E) and MMP-9 (B, D, F) in sequential sections obtained from primary melanomas and dermal metastases. The asterisks mark the melanocytes nests while the arrows indicate the stromal tissue. Original magnification X100. The IGFBP-3 and MMP-9 reactive cells were counted, and the scores determined, as described in Fig. 1 and in the Methods section.
Mentions: Secondly, tumour samples taken from patients were immuno-stained for both IGFBP-3 and MMP-9. As shown in Fig. 2 (C,D,E), the MMP-9 immunoreactivity of both tumor and stromal cells was significantly higher in metastatic lesions than in primary tumors. Strikingly, there was an almost perfect inverse correlation between the areas of low or no IGFBP-3 staining and those of high MMP-9 staining (Fig. 3), suggesting that the enzyme could indeed have a role in the degradation of IGFBP-3.

Bottom Line: 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.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 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.

View Article: PubMed Central - PubMed

Affiliation: Istituto Pasteur-Fondazione Cenci-Bolognetti, Dpt. Biotecnologie Cellulari ed Ematologia, University of Rome Sapienza, Rome, Italy.

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 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.

Show MeSH
Related in: MedlinePlus