Objectives Epithelial ovarian cancer (EOC) is the most lethal cancer among gynecological malignancies worldwide. The insulin-like growth factor (IGF) system plays a key role in regulating growth and invasiveness of EOC. IGF1R targeting showed anti-proliferative activity of EOC cells, however, clinical studies failed to show significant benefit. EOC cells suppress anti-tumor immune responses, by inducing Dendritic Cells (DCs) dysfunction. Interestingly, recent studies indicate that the IGF axis can regulate DCs maturation. Our study aims to evaluate the involvement and role of the IGF1 axis in DCs differentiation in EOC.
Methods Studies were conducted on EOC and a human monocyte cell lines. IGF1R expression levels were evaluated by Western blots. Differentiated DCs were treated with IGF1R inhibitor and co-cultured with EOC cell lines, thereafter scratch assay was performed. Tissue microarray was implemented on 40 paraffin blocks from EOC patients and expression of IGF1R associated proteins and DCs markers was evaluated by immunohistochemistry.
Results DCs differentiation was characterized by reduced in total IGF1R levels (50%) and phosphorylated IGF1R levels (95%). In addition, IGF1R inhibitor treated-DCs decreased EOC cell migration. TMA analysis demonstrated higher rate of strong IGF1R, p53 and PD-1 protein expression in patients with advanced-stage compared to early-stage, 87.5% vs 66.66%, 87.5% vs 75%, 62.5% vs 50%, respectively.
Conclusions IGF1R pathway inhibition in differentiated DCs suppressed EOC cell migration. Thus, restoring the anti-tumor immune response by IGF1R targeting may be an effective therapy for EOC. TMA analyses imply a correlation between IGF1R and PD-1 expression and EOC-stage, nonetheless, further evaluation is necessary.
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