Angiogenesis

Definition
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Growth and new formation of small blood vessels (capillaries), mainly by sprouting from a pre-formed capillary system. This must be distinguished from the formation of new blood vessels from the so-called endothelial precursor cells, which is known as vasculogenesis.

General information
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Angiogenesis is of considerable biological and medical importance. Especially solid tumors depend on a capillary network that grows with the tumor (tumor-induced angiogenesis or angioneogenesis). The vascular endothelial growth factor VEGF plays a central role in this process.

Increased expression of VEGF is associated with angiogenesis, malignancy, tumor progression and thus poor prognosis.

VEGF-neutralizing antibodies (s.a. Bevacizumab) play an essential role in the therapy of solid tumors today. They are in clinical trials in malignant melanoma. " Knockout mice" as animal models are frequently used in tumour research and enable the further development of newer antibodies.

Tyrosine kinase inhibitors such as imatinib also influence angiogenesis. Imatinib specifically blocks the binding site for ATP at the tyrosine kinase and inhibits the transfer of ATP phosphate groups to tyrosine residues of the substrate. Consecutively, signal transduction within the cells is sabotaged, resulting in disruption of proliferation, migration, invasion and angiogenesis. In addition to VEGF, there are other growth factors that regulate angiogenesis.

In 1984 a protein ( HGF = "hepatocyte growth factor") was detected for the first time, which is ubiquitously expressed by mesenchymal cells. It was given the name HGF because it was originally identified as a hepatically produced mitogen.

Note(s)
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Angiogenesis is a complex process in which endothelial cells, pericytes and smooth muscle cells are activated and proliferated by growth factors such as VEGF (Vascular Endothelial Growth Factor) or EGF (Epidermal Growth Factor). The subsequent conversion of the capillaries in arteries and veins is achieved by activating certain genes. The members of the Notch family are responsible for arteriogenesis. The formation of the veins is regulated by the COUP-TFII receptor, and the final wall formation is regulated by platelet-derived growth factor (PDGF) and angiopoietin-1.

Literature
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Bussolini F et al (1992) Hepatocyte growth factor is a potent angiongenic factor which stimulates endothelial cell motility and growth. J Cell Biol 119: 629-641
Goldman JM et al (2003) Chronic myeloid leukemia - advances in biology and new approaches to treatment. N Engl J Med 349: 1451-1464
Lin EY et al (2006) Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res 66: 11238-11246
Saltz LB et al (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22: 1201-1208