Nanopublications LDF server

Matches in Nanopublications for { <http://www.tkuhn.ch/bel2nanopub/RAw6FGtTK1x8oF9GcyH2uVk6XYSAF2fT9p7f9MGMdsYo4#_3> ?p ?o ?g. }

• _3 value "and also by oncogene activation or tumour-suppressor mutation (recently reviewed in REF. 10). The angiogenic switch can occur at different stages of the tumour-progression pathway, depending on the tumour type and the environment. It has been shown that dormant lesions, and, in some instances, premalignant lesions, also initiate neovascularization, which allows them to progress6,11. The fact that tumours are dependent on blood supply has inspired many researchers to search for anti-angiogenic molecules, and to design antiangiogenic strategies for cancer treatment. But what is the importance of the angiogenic switch in the tumour-progression pathway, and how is it regulated? Tumour versus physiological angiogenesis During embryonic vasculogenesis, blood vessels are formed de novo, from endothelial-cell precursors (angioblasts) that assemble into a primary capillary plexus. This primitive network then differentiates, and new blood vessels sprout and branch from pre-existing capillaries - the process of angiogenesis12. The vasculature is usually quiescent in the adult, and endothelial cells are among the longest-lived cells outside the nervous system. In fact, physiological endothelial-cell turnover is reportedly measured in years in tissues that do not require ongoing angiogenesis. The few adult tissues that do require ongoing angiogenesis include female reproductive organs, organs that are undergoing physiological growth11 or injured tissue. The point at which these 'normal' processes differ from pathological angiogenesis is in the tightly regulated balance of pro- and anti-angiogenic signals. During normal physiological angiogenesis, new vessels rapidly mature and become stable. By contrast, tumours - described as \"wounds that never heal\"13- have lost the appropriate balances between positive and negative controls. One characteristic feature of tumour blood vessels is that they fail to become quiescent, enabling the constant growth of new tumour blood vessels.Consequently, the tumour vasculature develops unique characteristics and becomes quite distinct from the normal blood supply system. Tumour blood vessels are architecturally different from their normal counterparts - they are irregularly shaped, dilated, tortuous and can have dead ends. They are not organized into definitive venules, arterioles and capillaries like their normal counterparts, but rather share chaotic features of all of them. The vascular network that forms in tumours is often leaky and haemorrhagic, partly due to the overproduction of vascular endothelial growth factor (VEGF; also known as vascular permeability factor, VPF). PERIVASCULAR CELLS, which are usually in close contact with the endothelium, often become more loosely associated or less abundant14,15. Tumour vessels have also been reported to have cancer cells integrated into the vessel wall16,17, and some tumours rely heavily on vasculogenesis, recruiting ENDOTHELIAL PRECURSOR CELLS from the bone marrow18. Blood flows irregularly in tumour vessels,moving more slowly and sometimes even oscillating. This leads to dysfunctional capillaries. Tumours can be quite heterogeneous in their vascular patterns, and are able to overproduce their capillary networks. In normal tissues, by contrast, vessel density is dynamically controlled by the metabolic needs of nutrients and oxygen. So, the structural and functional abnormalities in tumour vessels reflect the pathological nature of their induction. Although we do not fully understand the molecular controls of all of these abnormalities,we can surmise that they are the result of the imbalanced expression and function of angiogenic factors. How are tumour blood vessels formed? The vasculogenic process that is used by the early embryo has been adapted for use in adults, under certain situations, and by tumours. In this setting, endothelial precursor cells can be mobilized from the bone marrow and transported t..." provenance.
• _3 wasQuotedFrom 12778130 provenance.