Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Nat Commun. 2011;2:235. doi: 10.1038/ncomms1236.
Hamartomas are composed of cells native to an organ but abnormal in number, arrangement or maturity. In the tuberous sclerosis complex (TSC), hamartomas develop in multiple organs because of mutations in TSC1 or TSC2. Here we show that TSC2-null fibroblast-like cells grown from human TSC skin hamartomas induced normal human keratinocytes to form hair follicles and stimulated hamartomatous changes. Follicles were complete with sebaceous glands, hair shafts and inner and outer root sheaths. TSC2-null cells surrounding the hair bulb expressed markers of the dermal sheath and dermal papilla. Tumour xenografts recapitulated characteristics of TSC skin hamartomas with increased mammalian target of the rapamycin complex 1 (mTORC1) activity, angiogenesis, mononuclear phagocytes and epidermal proliferation. Treatment with an mTORC1 inhibitor normalized these parameters and reduced the number of tumour cells. These studies indicate that TSC2-null cells are the inciting cells for TSC skin hamartomas, and suggest that studies on hamartomas will provide insights into tissue morphogenesis and regeneration.
错构瘤由器官内固有细胞组成，但数量、排列或成熟异常。在结节性硬化症复合征（TSC）中，由于 TSC1 或 TSC2 的突变，错构瘤在多个器官中发展。在这里，我们表明，源自人 TSC 皮肤错构瘤的 TSC2 缺失成纤维样细胞可诱导正常人类角质形成细胞形成毛囊并刺激错构瘤样变化。毛囊完整，具有皮脂腺、毛干和内根鞘和外根鞘。围绕毛球的 TSC2 缺失细胞表达真皮鞘和真皮乳头的标志物。肿瘤异种移植物重现了 TSC 皮肤错构瘤的特征，表现为雷帕霉素复合物 1（mTORC1）活性增加、血管生成、单核吞噬细胞和表皮增殖。mTORC1 抑制剂的治疗使这些参数正常化，并减少肿瘤细胞数量。这些研究表明，TSC2 缺失细胞是 TSC 皮肤错构瘤的引发细胞，并表明对错构瘤的研究将为组织形态发生和再生提供深入了解。
