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

Our previous studies, revealed a dramatic degradation of the circulating IGF binding protein-3, one of the major regulators of IGF1, in the sera of patients affected by the IV stage of melanoma. For this reason, we focused on understanding the relation between IGFBP3 and melanoma cells. In "in vitro" experiments we found that the addition of exogenous IGFBP3 to the growth medium of metastatic melanoma cells is able to reduce their migratory and invasive potential. At the molecular level, the study of the molecular pathway involved in this process, revealed a strong dephosphorilation of AKT and GSK3β. Surprisingly, the nature of this dephosphorilation is not dependent on the IGF1 sequestration but, instead, on the activation of AKT's phosphatases that inhibit its activity. Additionally our group found an important anti-tumoral activity of IGFBP3 "in vivo". In fact mice, inoculated with melanoma cells, showed a reduction of the tumor's volume after the administration of the protein, making IGFBP3 a new candidate for therapeutic approach.