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Insulin-like growth factors (IGFs) system and tumors

Publication at Faculty of Medicine in Pilsen |
2016

Abstract

The interaction between growth factors and cancer incidence and development has been discussed recently. Insulin-like growth factors (IGF, insulin-like growth factors, formerly named somatomedines) are peptides, that participate on growth regulation, metabolism regulation, cell survival and differentiation.

They are regulated by growth hormone (GH). IGFs are synthesized in liver and they occur in other body fluids.

IGFBPs occur in different body fluids like serum, amniotic fluid and cerebrospinal fluid. IGFBPs are synthesized in liver.

These binding proteins serve as storage of IGFs in intercellular space. Effect of IGF1 and IGF2 on cell is mediated by receptors.

Signal transduction follows the successful binding to the receptor via signal intracellular pathway - i.e. cascade of enzymes and its substrates. Based on knowledge of IGF1 and IGF2 effect on cells it is assumed that high IGFs serum levels increase the risk for cancer development.

They also stimulate proliferation and risk of malignant transformation. High serum levels of binding proteins IGFBPs, particularly dominant serum binding protein IGFBP3, should decrease the risk and inhibit the cellular growth.

It is assumed that malignant transformation of the cells can occur independently from serum levels of IGFs in case of presence of functional IGF1R. Recent clinical studies confirmed that high circulating IGF1 concentrations and low IGFBP3 serum levels are related to increase risk for cancer diseases.

Negative correlation between IGFBP3 levels and risk of cancer diseases corresponds to protective role of IGFBP3.