Особенности ангиогенеза в молочной железе

В обзоре представлены современные данные об особенностях ангиогенеза в молочной железе, как в норме, так и в процессе развития опухоли. Общепризнано, что основными патогенетическими механизмами в процессе развития рака молочной железы являются ангиогенез и ремоделирование; дополнительную роль в формировании сосудистой сети при воспалительной форме рака молочной железы может играть сосудистая мимикрия. Подробный анализ такого рода информации

Characteristics of Angiogenesis in Mammary Gland

Changes of the angiogenic factors activity in healthy mammary gland is a normal physiological process controlled by sex hormones that affect the estrogen-sensitive element, which is localized in the gene for vascular endothelial growth factor (VEGF). Cyclical changes in the concentrations of VEGF take place in the healthy mammary gland in vivo during the menstrual cycle. So in the luteal phase, when estradiol and progesterone concentrations tend to increase, the concentration of VEGF in the extracellular space in tissues of the breast increased doubly. At the same time, significant changes in plasma levels of this factor was not observed. VEGF may be involved in the mechanisms that cause premenstrual mastalgia. Blood supply of the breast tumor may effects through several mechanisms. These include the remodeling of blood vessels, vasculogenesis, vascular glomerular mimicry and angiogenesis. Each of the mechanisms may be of particular value in a single type of tumor or at a certain stage of tumor development, but the relative role of each in human tumors is unknown. Key regulators of angiogenesis are vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), placental growth factor α (PDGF α), transforming growth factor β (TGF β), angiopoietin, and others, the main promoters of which are a series of mechanical and metabolic factors such as hypoxia. Hypoxia is characteristic of solid tumors. Hypoxia is an important inducer of the synthesis of VEGF. Its effect is mediated by hypoxia-inducible transcription factors 1α and 2α. The overexpression of HIF-1α and HIF-2α is the characteristic of the most tumor cells. Moreover, overexpression of HIF-α is associated with the growth rate and metastatic potential of tumors. Increasing the number of the HIF-1α-positive cells in breast cancer correlates with advanced stages of the disease and poor prognosis. The role of other VEGF family members is in the stage of identification. If an ability of the tumor to secrete VEGF-A is limited, other homologs of VEGF may be induced for the activation of the new blood vessels formation. Concentration of the VEGF-B, VEGF-C and VEGF-D is associated with the central metastatic disease, prognosis, and the density of lymph vessels.