The role of extracellular membrane matrix proteins and integrin alpha chains in three-dimensional capillary morphogenesis
Using siRNA technology, our studies show suppression of α 2 and α3 integrin subunits markedly blocks both EC capillary lumen formation and invasion, whereas suppression of the α 11 integrin subunit appears to promote EC invasion in model systems. Knockdown of type IV collagen, a major component in EC basement membranes, and type VI collagen, also showed inhibitory effects in EC capillary lumen formation and invasion. Additionally, siRNA directed to the α4 laminin chain, which has been shown to be important in microvessel stability, and the β2 aminin chain, which are both upregulated in DNA microarray studies, block EC capillary lumen formation and invasion as well. This work demonstrates that siRNA technology can be utilized to define the functional role of specific endothelial genes during capillary tube morphogenesis in 3D extracellular matrix environments, and validates a key role for specific integrin and basement membrane matrix genes in these events.
0379: Cellular biology