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

我们研究了人神经纤维瘤细胞对各种生长因子的生长反应，重点研究了肿瘤坏死因子α (tnf - α)在神经纤维瘤细胞增殖中的作用。tnf - α以剂量和时间依赖性的方式加速NF细胞的增殖，而其他生长因子不作为有丝分裂原。此外，tnf - α特异性地增强了神经纤维瘤细胞的有丝分裂活性，而对其他正常细胞和恶性细胞没有作用。诱导的增殖伴随着MEK/ERK和p38信号通路。抗tnf受体1中和单克隆抗体可减弱tnf - α的有丝分裂作用。tnf - α受体的表达在神经纤维瘤细胞和组织中得到证实，而tnf - α的产生主要在神经纤维瘤的肥大细胞中发现。来自肥大细胞的tnf - α可能在i型神经纤维瘤病中神经纤维瘤细胞的增殖中发挥重要作用。用特异性tnf - α和/或tnf - α受体抗体抑制tnf - α的作用可能有效抑制NF-1患者的神经纤维瘤生长。

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.