Modulation of VEGF signalling output by the Notch pathway
ABSTRACT The formation of blood vessels within the vascular system entails a variety of cellular processes, including proliferation, migration and differentiation. In many cases, these diverse processes need to be finely coordinated among neighbouring endothelial cells in order to establish a functional vascular network. For instance, during angiogenic sprouting specialized endothelial tip cells follow guidance cues and migrate extensively into avascular tissues while trailing stalk cells must stay connected to the patent blood vessel. The vascular endothelial growth factor (VEGF) and Notch signalling pathways have emerged as the major players in governing these different cellular behaviours. In particular, recent work indicates an important role for Notch signalling in determining how an endothelial cell responds to VEGF. In this review, we provide an overview of these biochemically distinct pathways and discuss how they may interact during endothelial cell differentiation and angiogenesis.
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ABSTRACT: Human cord blood (CB) is enriched in circulating endothelial colony forming cells (ECFCs) that display high proliferative potential and in vivo vessel forming ability. Because Notch signaling is critical for embryonic blood vessel formation in utero, we hypothesized that Notch pathway activation may enhance cultured ECFC vasculogenic properties in vivo.Cytotherapy 01/2015; DOI:10.1016/j.jcyt.2014.12.003 · 3.10 Impact Factor
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ABSTRACT: Research on the nanoscale membrane structures known as lipid rafts is relevant to the fields of cancer biology, inflammation and ischaemia. Lipid rafts recruit molecules critical to signalling and regulation of the invasion process in malignant cells, the leukocytes that provide immunity in inflammation and the endothelial cells that build blood and lymphatic vessels, as well as the patterning of neural networks. As angiogenesis is a common denominator, regulation of receptors and signalling molecules critical to angiogenesis is central to the design of new approaches aimed at reducing, promoting or normalizing the angiogenic process. The goal of this review is to highlight some of the key issues that indicate the involvement of endothelial cell lipid rafts at each step of so-called 'sprouting angiogenesis', from stimulation of the vascular endothelial growth factor to the choice of tip cells, activation of migratory and invasion pathways, recruitment of molecules that guide axons in vascular patterning and maturation of blood vessels. Finally, the review addresses opportunities for future studies to define how these lipid domains (and their constituents) may be manipulated to stimulate the so-called 'normalization' of vascular networks within tumors, and be identified as the main target, enabling the development of more efficient chemotherapeutics and cancer immunotherapies.Cellular and Molecular Life Sciences CMLS 01/2015; DOI:10.1007/s00018-014-1814-x · 5.86 Impact Factor
Cellular and Molecular Life Sciences CMLS 01/2015; · 5.86 Impact Factor