Extracellular angio-associated migratory cell protein plays a positive role in angiogenesis and is regulated by astrocytes in coculture

The extracellular form of angio-associated migratory cell protein (AAMP), a recently discovered protein, plays a positive role in angiogenesis and can be regulated by astrocytes. Angiogenic activities are inhibited by an affinity-purified, polyclonal antibody generated to recombinant AAMP. Inhibition of endothelial cell tube formation was previously shown and now endothelial cell migration assays using this antibody show dose-dependent inhibition (75%) of endothelial cell migration. Also, antisense inhibition has been used to determine the effects of reducing total AAMP (extracellular and intracellular forms). An AAMP-specific antisense oligonucleotide that targets a region near its amino terminus, anti-MES, inhibits (45%) total AAMP production by bovine aortic endothelial cells (BAECs), compared to a negative control oligonucleotide. Paradoxically, comparable use of antisense-MES results in a 27% increase in BAEC motility. Decreased cellular production of total AAMP (via antisense) that results in an increase of endothelial migration contrasts with antibody inhibition of extracellular AAMP that decreases migration. This indicates compartment-specific roles for AAMP in angiogenesis. Transwell cocultures of human astrocytes and BAECs increase (53%) the amount of extracellular AAMP found associated with endothelial cells. Therefore, regulation of extracellular AAMP by astrocytes is hypothesized to aid in angiogenesis of the nervous system. Extracellular AAMP's positive role may be either as a promoter or as a permissive protein in this process. (C) 2002 Elsevier Science (USA).