Detection and identification of oxidized insulin-like growth factor-binding proteins and receptors in patients with colorectal carcinoma
| Autor: | Olgica Nedić, Dragana Robajac, Goran Miljuš, Miloš Šunderić, Vesna Malenković, Blagoje Đukanović |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Proteolysis medicine.medical_treatment Oxidative phosphorylation Plasma protein binding Biochemistry Receptor IGF Type 2 Insulin-like growth factor-binding protein Receptor IGF Type 1 Cell membrane 03 medical and health sciences Insulin-like growth factor 0302 clinical medicine Somatomedins Physiology (medical) Internal medicine medicine Humans Receptor 030304 developmental biology 0303 health sciences medicine.diagnostic_test biology Chemistry Somatomedin 3. Good health Insulin-Like Growth Factor Binding Protein 2 Insulin-Like Growth Factor Binding Protein 3 medicine.anatomical_structure Endocrinology 030220 oncology & carcinogenesis biology.protein Colorectal Neoplasms Oxidation-Reduction Protein Binding |
| Zdroj: | Free Radical Biology and Medicine. 65:1195-1200 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2013.09.003 |
| Popis: | Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and also the one with the highest mortality rate. Tumor growth is assisted by various growth factors, and insulin-like growth factors (IGFs) are among the most important. A majority of the IGFs are bound to IGF-binding proteins (IGFBPs) and their release is dependent on the rate of IGFBP proteolysis. The action of free IGFs is exerted and controlled by binding to cell membrane receptors (IGF-Rs). The objective of this work was to connect two determinants of the CRC pathology: oxidation as a process that underlies tumor development and the members of the IGF system that control it. Carbonyl groups (CO) on IGFBP-2, IGFBP-3, IGF-1R, and IGF-2R were determined in samples obtained from patients with CRC, and IGF-binding properties of these proteins were analyzed. According to our results, IGFBP-2 and IGFBP-3 in serum had increased content of CO groups due to CRC. Oxidation of IGFBP-2 increased its affinity for IGF molecules, whereas oxidation of IGFBP-3 reduced it. As for receptors, only intact CO-IGF-2R was detected on solubilized colon membranes, whereas CO-IGF-1R was degraded into fragments. Oxidative changes in the IGF axis may be regarded as part of the mechanism of its action. IGFs bound to IGFBP-3 remain in the circulation, whereas those bound to IGFBP-2 freely reach target tissues. Therefore, oxidation supports IGF distribution toward tissues and, consequently, promotes tumor growth. |
| Databáze: | OpenAIRE |
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