Zheng Huarui, Chang Lou, Patel Neha, Yang Jiong, Lowe Lori, Burns Dennis K, Zhu Yuan
Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cancer Cell. 2008 Feb;13(2):117-28. doi: 10.1016/j.ccr.2008.01.002.
Recent evidence suggests that alterations in the self-renewal program of stem/progenitor cells can cause tumorigenesis. By utilizing genetically engineered mouse models of neurofibromatosis type 1 (NF1), we demonstrated that plexiform neurofibroma, the only benign peripheral nerve sheath tumor with potential for malignant transformation, results from Nf1 deficiency in fetal stem/progenitor cells of peripheral nerves. Surprisingly, this did not cause hyperproliferation or tumorigenesis in early postnatal period. Instead, peripheral nerve development appeared largely normal in the absence of Nf1 except for abnormal Remak bundles, the nonmyelinated axon-Schwann cell unit, identified in postnatal mutant nerves. Subsequent degeneration of abnormal Remak bundles was accompanied by initial expansion of nonmyelinating Schwann cells. We suggest abnormally differentiated Remak bundles as a cell of origin for plexiform neurofibroma.
最近的证据表明，干细胞/祖细胞自我更新程序的改变会导致肿瘤发生。通过利用1型神经纤维瘤病（NF1）的基因工程小鼠模型，我们证明了丛状神经纤维瘤，这是唯一具有恶性转化潜能的良性周围神经鞘瘤，是由周围神经胎儿干细胞/祖细胞中的Nf1缺陷引起的。令人惊讶的是，这在出生后早期并未导致过度增殖或肿瘤发生。相反，除了在出生后突变神经中发现的异常Remak束（无髓鞘轴突-施万细胞单元）外，在没有Nf1的情况下，周围神经发育在很大程度上似乎是正常的。异常Remak束的随后退化伴随着非髓鞘施万细胞的初始扩张。我们认为异常分化的Remak束是丛状神经纤维瘤的起源细胞。
