Additional Biologic Functions of VEGF

Besides its role as an essential regulator of physiological endothelial cell growth, permeability,

and migration in vitro and in vivo, - ' ' VEGF is a pivotal factor in hematopoiesis which affects the differentiation of multiple hematopoietic lineages.6'7'61'121 VEGF triggers the differentiation of hematopoietic and endothelial lineages from a common potential precursor cell within the blood islands, the hemangioblasts.61,174 Specifically, several recent reports show the importance of VEGF in erythroid differentiation.175 Moreover, VEGF mediates HSC survival and repopulation via an autocrine loop,121 whereas angiogenesis is regulated via a paracrine VEGF loop. Interestingly, the Drosophila PDGF/VEGFR (PVR) directly controls survival of a hemocyte cell line, thereby demonstrating a striking homology with mammalian hematopoiesis. This finding suggests Drosophila to be a useful model system for the study of hematopoietic cell survival in development and disease.176 In addition, VEGF inhibits maturation of dendritic cells through inhibition of nuclear factor-kB

1HH iao activation ; increases both osteoclastic bone-resorbing activity as well as osteoclast chemotaxis179; induces migration, parathyroid hormone (PTH)-dependent cAMP accumulation, and alkaline phosphatase in osteoblasts180; acts as an autocrine factor for osteoblast differentiation181; enhances natural killer (NK) cell adhesion to tumor endothelium182; recruits monocyte71 and endothelial cell progenitors148 to the vasculature; stimulates surfactant production by alveolar type II cells183; and mediates a direct neuroprotective effect on motor neurons in vitro.184 In the context of cancer, VEGF is an important growth, migration, and survival factor in Kaposi's sarcoma (KS) - ; as well as leukemia, and MM76,191 (Figure 4.2).

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