Immortalized rat Schwann cells produce tumoursin vivo

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Abstract
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 tumoursin 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. The cells in the tumour expressed the Schwann cell surface antigens laminin, 217C (Ran 1) and S-100 like the immortalized cells that had been injected. Within the tumour the cells were embedded in a collagenous matrix, were surrounded by basal lamina and occasionally attained an orientation comparable to the Antoni A or Antoni B patterns typical of human schwannomas. These data suggest that rat Schwann cells immortalizedin vitro by chronic mitogenic stimulation can provide an experimental animal model for human schwannomas and neurofibromas.