Evaluation of the Expression and Role of IGF Pathway Biomarkers in Human Sarcomas

Abstract

Recent studies have shown that insulin-like growth factor (IGF) signaling components have been involved in the pathogenesis and progression of different types of sarcomas. There has been some evidence to indicate the differential-expression of IGF2 and insulin-like growth factor 1 receptor (IGF1R) in human sarcomas. The present study utilized immunohistochemistry (IHC) and in situ hybridization (ISH) to determine the expression of IGF2 and IGF1R in eighty-two cases of human sarcoma specimens and eight cases of non-tumor tissue (NTT). IGF2/IGF1R signaling was blocked by recombinant adenovirus-mediated IGF1R small hairpin RNA (shIGF1R), which was used to transfect into human osteosarcoma (OS) MG-63 cells. The expression of IGF2, IGF1R, matrix metallopeptidase-2 (MMP-2) and MMP-9 was detected by Real-time PCR. Cell migration was evaluated by wound healing'assay. As a consequence, the expression of IGF1R and IGF2 was found in human OS with higher strong reactivity rate compared with the NTT (85.0% vs 50.0%, P = 0.022; 95.0% vs 100.0%, P = 0.042), elevating with the ascending order of tumor malignancy. Also, IGF1R had differential expression in different types of sarcomas ( P = 0.002), while IGF2 had no significant difference ( P = 0.105). Targeted blockade of IGF2/IGF1R signaling decreased the expression of IGF2, IGF1R, and MMP-2/-9, and diminished the migration capabilities of MG-63 cells. In conclusion, IGF1R is differentially-expressed in different types of human sarcomas, and targeted blockade of IGF1R pathway may inhibit human OS migration through down-regulation of MMP-2/-9 expression. IGF1R pathway may represent a significant therapeutic modality for the treatment of sarcomas.