Limits...
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.

Show MeSH

Related in: MedlinePlus

IGFBP-3 reduces motile and invasive behavior of melanoma cells.(A) First row: a representative migration pattern of human primary melanoma cells (WM793), either IGFBP-3-treated or untreated. Second and third row: migration pattern of human metastatic melanoma cells (Me501) untreated or treated with 2 µg/mL IGFBP-3. Fourth and fifth row: murine metastatic melanoma cells (B16), untreated or treated with 2 µg/mL IGFBP-3. Last two rows: Me501 cells treated with unspecific IgG or with 10 µg/mL of anti-IGFBP-3 antibody. Scratch-test assays were performed as described in the Methods and the images were captured at 0, 6, 24 h after incubation. All the experiments shown were repeated three or more times. (B) Left panel: invasiveness pattern of Me501 cells, untreated or treated for 48 h with the indicated doses of IGFBP-3. Right panel: invasiveness pattern of Me501 cells untreated or treated for 48 h with the indicated doses of anti-IGFBP-3 antibodies. Trans-well migration/invasion assays were performed as described in the Methods. Invasiveness assays were repeated three or more times.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4048209&req=5

pone-0098641-g004: IGFBP-3 reduces motile and invasive behavior of melanoma cells.(A) First row: a representative migration pattern of human primary melanoma cells (WM793), either IGFBP-3-treated or untreated. Second and third row: migration pattern of human metastatic melanoma cells (Me501) untreated or treated with 2 µg/mL IGFBP-3. Fourth and fifth row: murine metastatic melanoma cells (B16), untreated or treated with 2 µg/mL IGFBP-3. Last two rows: Me501 cells treated with unspecific IgG or with 10 µg/mL of anti-IGFBP-3 antibody. Scratch-test assays were performed as described in the Methods and the images were captured at 0, 6, 24 h after incubation. All the experiments shown were repeated three or more times. (B) Left panel: invasiveness pattern of Me501 cells, untreated or treated for 48 h with the indicated doses of IGFBP-3. Right panel: invasiveness pattern of Me501 cells untreated or treated for 48 h with the indicated doses of anti-IGFBP-3 antibodies. Trans-well migration/invasion assays were performed as described in the Methods. Invasiveness assays were repeated three or more times.

Mentions: For scratch-repair analysis, primary (WM793), and metastatic (Me501 and B16F10) melanoma cell lines were grown to confluence in 10% serum. After introduction of the scratch, the cells were supplemented with serum-free medium without or with added IGFBP-3 (2 ug/mL) and followed for up to 48 hours. As shown in Fig. 4A (first row), primary melanoma cells were scarcely mobile and did not appreciably migrate into the scratch; this motility pattern remained unchanged upon treatment with IGFBP-3 (not shown). By contrast, metastatic cells were highly mobile, migrating within the gap already after 6 hours and largely covering the wound in about 24 hours (Fig. 4A, second and fourth row). Strikingly, treatment with IGFPB-3 markedly retarded the migration of both human and murine melanoma cells (Fig. 4A, third and fifth row). Also, addition of anti-IGFBP-3 antibodies to the culture media, to sequester any cell-made IGFBP-3, accelerated scratch repair (Fig. 4A, last two rows).


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 reduces motile and invasive behavior of melanoma cells.(A) First row: a representative migration pattern of human primary melanoma cells (WM793), either IGFBP-3-treated or untreated. Second and third row: migration pattern of human metastatic melanoma cells (Me501) untreated or treated with 2 µg/mL IGFBP-3. Fourth and fifth row: murine metastatic melanoma cells (B16), untreated or treated with 2 µg/mL IGFBP-3. Last two rows: Me501 cells treated with unspecific IgG or with 10 µg/mL of anti-IGFBP-3 antibody. Scratch-test assays were performed as described in the Methods and the images were captured at 0, 6, 24 h after incubation. All the experiments shown were repeated three or more times. (B) Left panel: invasiveness pattern of Me501 cells, untreated or treated for 48 h with the indicated doses of IGFBP-3. Right panel: invasiveness pattern of Me501 cells untreated or treated for 48 h with the indicated doses of anti-IGFBP-3 antibodies. Trans-well migration/invasion assays were performed as described in the Methods. Invasiveness assays were repeated three or more times.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0098641-g004: IGFBP-3 reduces motile and invasive behavior of melanoma cells.(A) First row: a representative migration pattern of human primary melanoma cells (WM793), either IGFBP-3-treated or untreated. Second and third row: migration pattern of human metastatic melanoma cells (Me501) untreated or treated with 2 µg/mL IGFBP-3. Fourth and fifth row: murine metastatic melanoma cells (B16), untreated or treated with 2 µg/mL IGFBP-3. Last two rows: Me501 cells treated with unspecific IgG or with 10 µg/mL of anti-IGFBP-3 antibody. Scratch-test assays were performed as described in the Methods and the images were captured at 0, 6, 24 h after incubation. All the experiments shown were repeated three or more times. (B) Left panel: invasiveness pattern of Me501 cells, untreated or treated for 48 h with the indicated doses of IGFBP-3. Right panel: invasiveness pattern of Me501 cells untreated or treated for 48 h with the indicated doses of anti-IGFBP-3 antibodies. Trans-well migration/invasion assays were performed as described in the Methods. Invasiveness assays were repeated three or more times.
Mentions: For scratch-repair analysis, primary (WM793), and metastatic (Me501 and B16F10) melanoma cell lines were grown to confluence in 10% serum. After introduction of the scratch, the cells were supplemented with serum-free medium without or with added IGFBP-3 (2 ug/mL) and followed for up to 48 hours. As shown in Fig. 4A (first row), primary melanoma cells were scarcely mobile and did not appreciably migrate into the scratch; this motility pattern remained unchanged upon treatment with IGFBP-3 (not shown). By contrast, metastatic cells were highly mobile, migrating within the gap already after 6 hours and largely covering the wound in about 24 hours (Fig. 4A, second and fourth row). Strikingly, treatment with IGFPB-3 markedly retarded the migration of both human and murine melanoma cells (Fig. 4A, third and fifth row). Also, addition of anti-IGFBP-3 antibodies to the culture media, to sequester any cell-made IGFBP-3, accelerated scratch repair (Fig. 4A, last two rows).

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