Analysis of the role of tumor necrosis factor alpha in proliferation of neurofibroma cells

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We investigated the growth responses of human neurofibroma cells to various growth factors and focused on the role of tumor necrosis factor alpha (TNF-alpha) in proliferation of neurofibroma cells. Proliferation of NF cells was accelerated by TNF-alpha in dose-and time-dependent manners whereas other growth factors did not serve as the mitogen. Furthermore, TNF-alpha specifically enhanced the mitogenic activity of neurofibroma cells but not other normal and malignant cells. Elicited proliferation was accompanied by MEK/ERK and p38 signaling pathway.The TNF-alpha mitogenic effect was attenuated by anti-TNF receptor 1 neutralizing monoclonal antibody. Whereas expression of TNF-alpha receptor was confirmed in neurofibroma cells and tissues, TNF-alpha production was found mainly in mast cells within neurofibroma.TNF-alpha derived from mast cells may play an important role in the proliferation of neurofibroma cells in neurofibromatosis type I. Inhibition of the TNF-alpha action with specific TNF-alpha and/or TNF-alpha receptor antibody might lead to efficacious suppression of neurofibroma growth in NF-1 patients.