Modulation of growth factor induced fiber outgrowth in rat pheochromocytoma (PC12) cells by a fibronectin receptor antibody

Rat pheochromocytoma PC12 cells respond to the binding of nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) by extending neurites in a manner resembling sympathetic neurons. This response requires cell attachment to an appropriate substratum (Fujii et al., J. Neurosci., 2:1157, 1982); attachment factors which function in this capacity include the adhesive proteins fibronectin and laminin. Incubating PC12 cells with a ployclonal antiserum directed against a putative 140‐kDa fibroblast cell surface fibronectin receptor (anti‐gp140) perturbed spreading but not attachment of the cells to fibronectin and laminin substrates. However, in the presence of anti‐gp 140 or its Fab fragments, NGF‐stimulated neurite outgrowth was dramatically reduced. The antibody also caused a retraction of previously extended neurites. SDS‐PAGE analysis of immunoprecipitates of PC12 cells surface labeled with 125I identified a prominent 120–140‐kDa band, suggesting that the site of anti‐gp 140 action in PC12 cells is also through a fibronectin receptor.