Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.
Am J Pathol. 2011 Feb;178(2):500-5. doi: 10.1016/j.ajpath.2010.10.041.
Cutaneous neurofibromas are the hallmarks of neurofibromatosis type 1 (NF1). They are composed of multiple cell types, and traditionally they are believed to arise from small nerve tributaries of the skin. A key finding in the context of this view has been that subpopulations of tumor Schwann cells harbor biallelic inactivation of the NF1 gene (NF1(-/-)). In the present study, our aim was to clarify further the pathogenesis of cutaneous neurofibromas. First, we detected cells expressing multipotency-associated biomarkers in cutaneous neurofibromas. Second, we developed a method for isolating and expanding multipotent neurofibroma-derived precursor cells (NFPs) from dissociated human cutaneous neurofibromas and used it to analyze their growth and differentiation potential. In analogy to solitary cells resident in neurofibromas, NFPs were found to express nestin and had the potential to differentiate to, at least, Schwann cells, neurons, epithelial cells, and adipocytes. Mutation analysis of the NFPs revealed that their genotype was NF1(+/-). The results led us to speculate that the development of cutaneous neurofibromas includes the recruitment of multipotent NF1(+/-) precursor cells. These cells may be derived from the multipotent cells of the hair roots, which often are intimately associated with microscopic neurofibromas.
皮肤神经纤维瘤是神经纤维瘤病 1 型 (NF1) 的特征。它们由多种细胞类型组成，传统上被认为起源于皮肤的小神经分支。在这种观点的背景下，一个关键的发现是肿瘤施万细胞的亚群携带 NF1 基因的双等位基因失活 (NF1(-/-))。在本研究中，我们的目的是进一步阐明皮肤神经纤维瘤的发病机制。首先，我们检测了皮肤神经纤维瘤中表达多能性相关生物标志物的细胞。其次，我们开发了一种从分离的人皮肤神经纤维瘤中分离和扩增多能神经纤维瘤衍生前体细胞 (NFPs) 的方法，并利用它来分析它们的生长和分化潜能。与神经纤维瘤中的常驻单一细胞类似，NFPs 表达巢蛋白，并且具有分化为至少施万细胞、神经元、上皮细胞和脂肪细胞的潜能。对 NFPs 的突变分析表明，它们的基因型为 NF1(+/-)。这些结果使我们推测皮肤神经纤维瘤的发生包括募集多能 NF1(+/-)前体细胞。这些细胞可能来源于毛囊的多能细胞，而毛囊通常与微小的神经纤维瘤密切相关。
