For the vascular-disruption analysis, cells were allowed to undergo morphogenesis and form capillary-like structures for 6 h before drug treatment was initiated.
In vitro, active Cdc42 improved coordination between actin filaments and microtubules and enhanced formation of vascular cords, suggesting that active Cdc42 rectifies defects in angiogenesis by improving cytoskeletal dynamics and capillary morphogenesis.
In vitro co-culture and matrigel plug assays demonstrated that PDAC cell-derived Shh induced Ang-1 and IGF-1 production in BMPCs, resulting in their enhanced migration and capillary morphogenesis activity.
PA can associate with two cell surface receptors, tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2) [7], [7], and possibly with the co-receptor low-density lipoprotein receptor-related protein LRP6 [8]–[10].
The first of these showed decreased urokinase plasminogen activator dependent invasion, proliferation, and capillary morphogenesis, and increased MMP-12 in SSc endothelial cells [ 46].
Since pent(r)axin 3 was up-regulated in SSc-MVECs, we added SSc-MVEC conditioned medium to N-MVECs for 24 hours, which resulted in a relevant inhibition of both invasion and capillary morphogenesis of N-MVECs.
The toxin has three components: the cell-binding moiety protective antigen (PA), LF, and edema factor (EF). Upon binding of PA to the cellular receptors (tumor endothelial marker 8 and capillary morphogenesis gene 2), it is cleaved and thereby activated by host furin and furin-like proteinases.
Previous studies have implicated FAK signaling as an important regulator of Rac activation in other cell types (Choma et al., 2007; Schaller, 2010) and Rac has been reported to regulate endothelial cell proliferation (Mettouchi et al., 2001), migration and capillary morphogenesis (Soga et al., 2001; Connolly et al., 2002).
RAD16-II stimulated spontaneous capillary morphogenesis, and increased β3 integrin phosphorylation and VEGF expression in MVECs.
These findings validate the utility of this material platform to decipher how the ECM regulates capillary morphogenesis and to support the formation of vascularized tissue constructs for potential applications in regenerative medicine.
