A novel signaling pathway regulates colon cancer angiogenesis through Norrin.

Norrin binds to the frizzled-4 receptor, stimulating canonical Wnt signaling. We investigate here the role of colorectal cancer (CRC) produced Norrin in endothelial cell growth, motility, and blood vessel formation, as well as the expression of the Norrin signaling pathway components in the CRC tumor microenvironment. Norrin conditioned medium produced by CRC cell line CaCO2 transfected with Norrin expression construct increased endothelial cell motility. Blocking Norrin signaling reduced endothelial cell motility, branch point number (1/mm(2)), and the network length (mm/mm(2)) during in vitro angiogenesis. Colorectal tumors express Norrin protein. Endothelial cells in the colorectal tumor microenvironment contain all of the components of the Norrin signaling pathway needed to respond to Norrin protein. This study presents data that Norrin may play a role in the regulation of angiogenesis in the colorectal cancer tumor microenvironment.