The Role Of Regulatory VEGF/VRGF-R1-System In Tumor Angiogenesis (A Literature Review)
Angiogenesis plays a major role in the functioning of the organism, therefore any type of disruption in its regulation results in severe consequences. Tumor in which the balance between pro-angiogenic and anti-angiogenic factors is shifted in favor of the former factors, is a proof of this fact. Vascular endothelial growth factor (VEGF) is a key protein that stimulates the formation of blood vessels. Moreover, its biological effects depend on the interaction with a corresponding receptor (VEGF-R1, -R2, -R3 ). Findings on VEGF- R1 appear to be the most contradictory: neither its tissue specificity nor its cellular localization have been identified yet. Furthermore, different isoforms of this receptor can display both pro- and anti-angiogenic properties. Full size membrane - associated mVEGF-R1 promotes proper blood vessel maturation in the process of embryogenesis, while truncated, soluble sVEGF-R1, on the contrary, inhibits angiogenesis. In addition, VEGF-R1 functions are not limited to «vascular» effects. Thus, receptor type 1 is expressed by many tumor cells and is responsible for their survival, migration, invasion and metastasis. The most recent data on co-localization of VEGF-R1 with nuclear lamina are ofparticular interest. Such localization of receptor type 1 allows it to bind to a ligand directly inside the cell, and it is necessary to consider this in the development of anti-angiogenic drugs. Expression of VEGF-R1 in tumor cells and its important role in their progression strongly suggest that receptor type 1 can be considered as a prospective target in cancer therapy in the future.