Release of autocrine growth factor by primary and immortalized Schwann cells

Schwann cells derived from neonatal rat sciatic nerve are quiescent in culture unless treated with specific mitogens. The use of glial growth factor (GGF) and forskolin has been found to be an effective method for stimulating proliferation of Schwann cells on a poly(L-lysine) substratum while maintaining their ability to myelinate axons in vitro. We find that repetitive passaging of Schwann cells with GGF and forskolin results in the loss of normal growth control; the cells are able to proliferate without added mitogens. The immortalized cells grow continuously in the absence of added growth factor and in the presence or absence of serum yet continue to express distinctive Schwann cell-surface antigens. The cells can associate with axons in culture, deposit a basal lamina, and ensheath axons, but they gradually lose their capacity to myelinate axons. The immortalized cells release growth-promoting activity into their culture medium. The released activity is effective in stimulating proliferation of primary Schwann cells that retain normal growth properties. Extracellular matrix molecules (laminin and fibronectin) augment the response of primary Schwann cells to the secreted mitogen. Quiescent primary Schwann cells also secrete a growth factor into their culture medium, but its activity is detectable only in the presence of added laminin or fibronectin. The results suggest that both normal and immortalized Schwann cells secrete an autocrine growth factor. Response to the autocrine factor appears to entail a multicomponent mechanism. Unlike primary cells, immortalized Schwann cells have the capacity to secrete all of the necessary components and to respond to them constitutively.