Role of insulin-like growth factor-1 (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers

The identification of novel autocrine/paracrine signaling pathways and possible markers represents an important component in the understanding of tumor growth control. in this study we assessed the potential role of Insulin-like Growth Factor-1 (IGF-1), the IGF-1 receptor (IGF-IR) and IGF binding protein-2 (IGFBP-2) in human colorectal cancer. initial studies demonstrating increased IGF-1 binding and IGF-IR density in human colon cancer tissue revealed that a component of iodinated (3-[125-1]iodotyrosyl) IGF-l (I-125-IGF-1) binding was not attributable to IGF-IR. Binding studies and Western plot analysis suggested that this second component of I-125-IGF-1 binding could be due to IGFBP-2. Further analysis by a specific solution hybridization/RNase protection assay for IGF-IR mRNA levels, IGFBP-2 mRNA levels and in situ hybridization for IGFBP-2 localization, was carried out in nine patients with colon cancer. IGF-IR mRNA levels by RNAse protection assays were unchanged, whereas IGFBP-2 mRNA levels were increased 4-8 fold in patients with colon cancer compared to controls. Three patients with Dukes stage C disease had the highest levels of IGFBP-2 mRNA. In situ hybridization studies localized IGFBP-2 mRNA to malignant cells and not to the surrounding stromal cells, suggesting an autocrine role for IGFBP-2. The discrepancy between increased IGF-1 binding, IGF-IR density, IGFBP-2 mRNA and the minimal modulation of the IGF-IR mRNA implies post transcriptional regulation of IGF-IRs. Our results suggest that IGFBP-2 may be implicated in colon cancer metastases and prognosis. Its usefulness as a potential tumor marker should be further investigated.