Correlation between insulin-like growth factor binding protein-3 serum level and melanoma progression

Panasiti, Vincenzo; Naspi, Antimo; Devirgiliis, Valeria; Curzio, Michela; Roberti, Vincenzo; Curzio, Gianfranca; Gobbi, Silvia; Calvieri, Stefano; Londei, Paola

doi:10.1016/j.jaad.2010.03.035

Cited by 11 publications

(13 citation statements)

References 16 publications

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“…2B). This result agrees with our previous finding that recombinant IGFBP-3 was degraded upon incubation with blood serum from stage-IV melanoma patients [15].…”

Section: Resultssupporting

confidence: 93%

“…In a previous work, we showed that serum levels of IGFBP-3 are lowered significantly in stage-IV melanoma patients [15]. Here, we have confirmed and extended those results, examining a larger number of patients and following over time a number of them.…”

Section: Resultssupporting

confidence: 87%

“…Many studies have shown its capacity to inhibit proliferation of breast, lung and prostate cancer cells [12]–[14]. In a previous report, we have shown that a strong correlation exists between the serum concentration of full-size, glycosylated IGFBP-3 and disease progression in melanoma patients [15]. In this study, we have investigated the effect of administering recombinant IGFBP-3 to cell cultures from primary and metastatic melanoma, from both human and murine sources.…”

Section: Introductionmentioning

confidence: 97%

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Insulin-Like-Growth-Factor-Binding-Protein-3 (IGFBP-3) Contrasts Melanoma Progression In Vitro and In Vivo

et al. 2014

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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.

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“…2B). This result agrees with our previous finding that recombinant IGFBP-3 was degraded upon incubation with blood serum from stage-IV melanoma patients [15].…”

Section: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Insulin-Like-Growth-Factor-Binding-Protein-3 (IGFBP-3) Contrasts Melanoma Progression In Vitro and In Vivo

et al. 2014

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“…Although most investigators have reported a positive association between IGF1 level (or IGF1/IGFBP3 ratio) and cancer risk, others have reported significant inverse associations, including in prostate cancer (Alokail et al 2011) and melanoma (Panasiti et al 2011, Park et al 2011b, for example. In addition, whereas large increases in IGFBP1 were reported to significantly raise the risk of overall cancer mortality in patients (Kaplan et al 2012), global Igfbp1 deletion does not affect prostate cancer development in a c-Myc transgenic mouse model (Gray et al 2011).…”

Section: Ilp Molecules and Cancer Riskmentioning

confidence: 99%

Insulin resistance and cancer: the role of insulin and IGFs

Djiogue¹,

Kamdje²,

Vecchio³

et al. 2012

Endocrine-Related Cancer

232

188

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Insulin, IGF1, and IGF2 are the most studied insulin-like peptides (ILPs). These are evolutionary conserved factors well known as key regulators of energy metabolism and growth, with crucial roles in insulin resistance-related metabolic disorders such as obesity, diseases like type 2 diabetes mellitus, as well as associated immune deregulations. A growing body of evidence suggests that insulin and IGF1 receptors mediate their effects on regulating cell proliferation, differentiation, apoptosis, glucose transport, and energy metabolism by signaling downstream through insulin receptor substrate molecules and thus play a pivotal role in cell fate determination. Despite the emerging evidence from epidemiological studies on the possible relationship between insulin resistance and cancer, our understanding on the cellular and molecular mechanisms that might account for this relationship remains incompletely understood. The involvement of IGFs in carcinogenesis is attributed to their role in linking high energy intake, increased cell proliferation, and suppression of apoptosis to cancer risks, which has been proposed as the key mechanism bridging insulin resistance and cancer. The present review summarizes and discusses evidence highlighting recent advances in our understanding on the role of ILPs as the link between insulin resistance and cancer and between immune deregulation and cancer in obesity, as well as those areas where there remains a paucity of data. It is anticipated that issues discussed in this paper will also recover new therapeutic targets that can assist in diagnostic screening and novel approaches to controlling tumor development.

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“…Indeed, many tumours are known to secrete both RNA and proteins that may act either locally or systemically. For instance, we have shown in the past that metastatic melanoma cells degrade insulin-like growth factor binding protein-3, a circulating and tissue protein with marked antitumoural properties, and that stage IV melanoma patients undergo a marked loss of serum insulin-like growth factor binding protein-3 [23]. Thus, a cancer may reach a threshold volume over which the concentration of cancer-produced molecules becomes capable of exerting systemic effects on the organism.…”

Section: Discussionmentioning

confidence: 99%

Metastatic Volume: An Old Oncologic Concept and a New Prognostic Factor for Stage IV Melanoma Patients

et al. 2013

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Background: The last melanoma staging system of the 2009 American Joint Committee on Cancer takes into account, for stage IV disease, the serum levels of lactate dehydrogenase (LDH) and the site of distant metastases. Objective: Our aim was to compare the significance of metastatic volume, as evaluated at the time of stage IV melanoma diagnosis, with other clinical predictors of prognosis. Methods: We conducted a retrospective multicentric study. To establish which variables were statistically correlated both with death and survival time, contingency tables were evaluated. The overall survival curves were compared using the Kaplan-Meier method. Results: Metastatic volume and number of affected organs were statistically related to death. In detail, patients with a metastatic volume >15 cm³ had a worse prognosis than those with a volume lower than this value (survival probability at 60 months: 6.8 vs. 40.9%, respectively). The Kaplan-Meier method confirmed that survival time was significantly related to the site(s) of metastases, to elevated LDH serum levels and to melanoma stage according to the latest system. Conclusion: Our results suggest that metastatic volume may be considered as a useful prognostic factor for survival among melanoma patients.

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Correlation between insulin-like growth factor binding protein-3 serum level and melanoma progression

Cited by 11 publications

References 16 publications

Insulin-Like-Growth-Factor-Binding-Protein-3 (IGFBP-3) Contrasts Melanoma Progression In Vitro and In Vivo

Insulin-Like-Growth-Factor-Binding-Protein-3 (IGFBP-3) Contrasts Melanoma Progression In Vitro and In Vivo

Insulin resistance and cancer: the role of insulin and IGFs

Metastatic Volume: An Old Oncologic Concept and a New Prognostic Factor for Stage IV Melanoma Patients

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