Immortalized rat Schwann cells produce tumours in vivo

We have recently reported the immortalization of primary Schwann cells isolated from sciatic nerves of normal neonatal rats. The cells were maintained under continuous mitogenic stimulation with glial growth factor and forskolin, achieving immortalization after 12 to 15 weeks without the use of viral infection, oncogene transformation or chemical carcinogens. The immortalized cells (1.17 cells) initially retain the capability to recognize and attach to peripheral neurons in culture as well as the ability to myelinate those neurons. The functional capacity of the cells gradually diminishes in culture, such that late passage cells can ensheath neurons but cannot form a myelin sheath. Both normal and immortalized cells secrete comparable amounts of autocrine growth factor activity in culture that can be regulated by extracellular matrix proteins. The difference between quiescent and immortalized Schwann cells seems to lie not in the production of growth factor but rather in the relative ability to respond to the factor(s). To test the potential of the immortalized Schwann cells for the ability to form tumours in vivo, we injected equal numbers of primary or immortalized Schwann cells into the sciatic nerve of adult syngenic rats and allowed them to incubate there for 6 to 13 weeks, whereupon the injected nerves were inspected for tumour formation. In every case (N = 3) the primary cells had no effect whereas every injection of immortalized cells (N = 5) resulted in a solid cellular mass surrounding the injected nerve. The tumours were encapsulated masses of actively dividing Schwann-like cells that surrounded but did not invade the nerve fascicle.(ABSTRACT TRUNCATED AT 250 WORDS)