Molecular forms of the insulin-like growth factor-binding protein-2 in patients with colorectal cancer

Abstract

The components of the insulin-like growth factor (IGF) system and molecules with which they interact are associated with the neoplastic transformation of cells in colorectal cancer. The IGF-binding protein-2 (IGFBP-2) plays a significant role in mitotic stimulation of the cancer cells and its concentration is significantly elevated in tumor states. Little is known about IGFBP-2 at the molecular level and the purpose of this study was to examine the interactions between IGFBP-2 and some other proteins, the fragmentation pattern and posttranslational modifications that might have occurred due to a disease. Results have shown that the amount of monomer IGFBP-2 was 20–30% greater in patients with cancer and the amount of fragmented IGFBP-2 was doubled compared to healthy people, whereas the portion of IGFBP-2 in complex with α2 macroglobulin (α2M) was 2.5 times lower in cancer patients. According to this distribution, IGFBP-2 was not only increasingly synthetized in patients with cancer, but also the amount involved in complexes with α2M was reduced favoring the existence of binary IGFBP-2/IGF complexes, free to leave the circulation. Both IGFBP-2 and α2M were significantly more oxidized in patients with colon cancer than in healthy individuals and α2M was additionally sialylated. It can be speculated that the formation of IGFBP-2/α2M complexes is part of the control mechanism involved in the regulation of IGFBP-2 and, consequently, IGF availability. It also seems that posttranslational modifications are more important factors in determining the amount of IGFBP-2/α2M complexes than the actual quantity of these two proteins.