Netrins are secreted molecules and involved in axon guidance, cell migration and
tumor development. Recent studies revealed that
netrins perform novel functions in such processes as epithelial development and angiogenesis without operating through the classical
netrin receptors, DCC (Deleted in
Colorectal Cancer) and Unc5h. In the present study, we investigated the roles of
netrin-1 and its receptors in cell spreading of human
glioblastoma cells, and found that
netrin-1 haptotactically enhanced
fibronectin-induced cell spreading and focal adhesion formation in U373
glioblastoma cells.
Netrin-1 binding to the U373 cell membrane was blocked by an antibody against
alphav integrin subunit, but not by an anti-DCC or anti-Unc5h antibody. In addition, enhancement of the
fibronectin response by
netrin-1 was abrogated by a function blocking antibody against
integrin alphavbeta3. Since the alphav subunit of the
integrin family plays an important role in the pathophysiological aspects of cell migration, including
tumor angiogenesis and
metastasis, our data provide important insight into the molecular mechanism of
netrin function.