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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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IGFBP-3 does not alter cell proliferation.Cell-cycle distribution evaluated by FACS analysis of Me501cells untreated or treated with IGFBP-3. The areas of the peaks corresponding to each phase were evaluated and plotted as an histogram. The experiment was performed in triplicate.
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pone-0098641-g005: IGFBP-3 does not alter cell proliferation.Cell-cycle distribution evaluated by FACS analysis of Me501cells untreated or treated with IGFBP-3. The areas of the peaks corresponding to each phase were evaluated and plotted as an histogram. The experiment was performed in triplicate.

Mentions: Importantly, the effect of IGFBP-3 on both migration and invasion was independent of cell proliferation. FACS analyses performed on semi-confluent cells did not reveal any difference in cell-cycle distribution between the IGFBP-3 treated and untreated cells (Fig. 5). As expected in dearth of serum, both groups underwent cell-cycle arrest after a while, but the timing of the arrest was unaffected by IGFBP-3 treatment. Furthermore, the amount of cells in sub-G1 was similar in treated and untreated samples, indicating that IGFBP-3 did not induce any significant apoptosis. This was confirmed by measurements of the apoptotic marker annexin-V, which remained unchanged upon IGFBP-3 treatment (not shown).


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)

IGFBP-3 does not alter cell proliferation.Cell-cycle distribution evaluated by FACS analysis of Me501cells untreated or treated with IGFBP-3. The areas of the peaks corresponding to each phase were evaluated and plotted as an histogram. The experiment was performed in triplicate.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0098641-g005: IGFBP-3 does not alter cell proliferation.Cell-cycle distribution evaluated by FACS analysis of Me501cells untreated or treated with IGFBP-3. The areas of the peaks corresponding to each phase were evaluated and plotted as an histogram. The experiment was performed in triplicate.
Mentions: Importantly, the effect of IGFBP-3 on both migration and invasion was independent of cell proliferation. FACS analyses performed on semi-confluent cells did not reveal any difference in cell-cycle distribution between the IGFBP-3 treated and untreated cells (Fig. 5). As expected in dearth of serum, both groups underwent cell-cycle arrest after a while, but the timing of the arrest was unaffected by IGFBP-3 treatment. Furthermore, the amount of cells in sub-G1 was similar in treated and untreated samples, indicating that IGFBP-3 did not induce any significant apoptosis. This was confirmed by measurements of the apoptotic marker annexin-V, which remained unchanged upon IGFBP-3 treatment (not shown).

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