The overall objective is to study the role of hormones and other growth factors in modulating the growth of the tumors associated with the genetic disorder neurofibromatosis (NF). For human meningiomas, we plan to compare the levels of steroid hormone binding by the tumors with their response to the hormones or their antagonists in culture. This will be correlated with the presence or absence of an abnormality of chromosome 22 as detected by karyotypes of early cell cultures and restriction enzyme analysis of DNA isolated directly from tumors. For human Schwann cell tumors (neurofibromas, acoustic neuromas, neurofibrosarcomas) we shall investigate and further characterize the high levels of glial growth factor(GGF)-like activity we have noted in these tumors. We will assess if GGF activity is made in culture by these cells and determine the effects of GGF, sex steroid hormones, and thyroid hormone or their blockers on Schwann cell growth. Further we shall induce Schwann cell tumors in rats with methylnitrosourea and use this model to study the presence of GGF in these tumors and the in vivo effects of the hormonal manipulations noted above. At present there is no medical treatment for NF or for its associated tumors. The development of medical methods to alter tumor growth would benefit not only patients with NF but also non-NF patients with spontaneous tumors of these cell types.
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