Insulin-like growth factors (IGFs) regulate the proliferation, differentation, apoptose, cell adhesion and metabolism in various tissues and cell types. The IGF-I, which is produced mainly in liver under the influence of Growth Hormone (GH), regulates as hormone the linear growth of the bones and the process of sexual maturity, while IGF-II is mainly a growth factor of foetal tissue. The biological actions of IGF over the IGF-Type-I receptor are modulated variably through the IGF binding proteins (IGFBP-1 to-6). IGFBP-2 is, after IGFBP-3, the second most frequent IGFBP in the human blood. IGFs, especially tumor typical pro-IGF-forms and hormones regulate the expression of IGFBP-2, GH effect is thereby inhibiting. At cellular level IGFBP-2 seems to stimulate the proliferation and dissemination of solid tumors via an IGF-independent mechanism.
IGFBP-2 is an unglycosylated polypetide of 31.3 kDa, which forms binary IGF-complexes and shows no circadian rhythm in the circulation.
The serum concentration of IGFBP-2 increases in fasting, after major surgery and after trauma, but the increasing of the concentration is most intensive in malignant diseases. The correlation of the IGFBP-2 level to the degree of progression is a striking feature in various tumor types as is the normalization of the IGFBP-serum levels after remission. During the GH-therapy, e.g. in short stature and in GH-abuse (doping) the IGFBP-2 level decreases. In Trisomy 18 IGFBP-2 in maternal serum is decreased and IGFBP-1 is increased; therefore the ratio IGFBP-2 /IGFBP-1 is a marker for this chromosome abnormality.
Transgenic organisms are a good opportunity to investigate the function of genes or proteins. The mouse model is a well-suited system for investigation of the relevance of IGFBP-2 in physiological and pathological processes. Over expression of the IGFBP-2 gene in mice results in a weight reduction of 30% in spleen and moderately reduced weight in other organs. Effects of IGFBP-2 on the organism can be compensated through the modified expression of other IGF-Binding proteins.
Especially in tumor biology the mouse system enables investigation of the systemic relevance of IGFBP-2. IGFBP-2 influences tumor cells as it induces catalase activity in adrenocortical cells. Furthermore IGFBP-2 interacts with tumor cells via its RGD-amino acid sequence and seems to stimulate cell invasion of glioma cells.
RP23-50H13.1; C330012H03Rik; IMP-2; Imp2; Neilsen; IGF-II mRNA-binding protein 2; IGF2 mRNA-binding protein 2; VICKZ family member 2; insulin-like growth factor 2 mRNA-binding protein 2; insulin-like growth factor 2, binding protein 2; IGF2BP2; insulin-like growth factor 2 mRNA binding protein 2; IGF II mRNA binding protein 2; IMP 2; hepatocellular carcinoma autoantigen p62; p62; VICKZ2