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Hair follicle differentiation-specific keratin expression in human basal cell carcinoma.

毛囊分化特异性角蛋白在人基底细胞癌中的表达。

  • 影响因子:1.09
  • DOI:10.1111/ced.14113
  • 作者列表:"Morgan HJ","Benketah A","Olivero C","Rees E","Ziaj S","Mukhtar A","Lanfredini S","Patel GK
  • 发表时间:2020-06-01
Abstract

BACKGROUND:Identification of human basal cell carcinoma (BCC) cancer stem cells and cellular hierarchy inherently implies the presence of differentiation. By conventional histological analysis, BCC demonstrates tumour nodules that appear relatively homogeneous. AIM:As BCCs arise from hair follicle (HF) keratinocytes, we sought to define the pattern of HF differentiation. METHODS:BCC, squamous cell carcinoma (SCC) and normal skin tissues were analysed using a microarray chip. The expression of individual keratins, regulatory pathways and proliferative states were analysed using reverse transcription-PCR and immunofluorescence microscopy. RESULTS:Microarray analysis of BCC, SCC and normal hair-bearing skin revealed that BCCs express a wide range of HF genes, including HF- specific keratins. BCC demonstrated outer (KRT5, KRT514, KRT516, KRT517 and KRT519) and inner (KRT25, KRT27, KRT28, KRT32, KRT35, KRT71, KRT75 and KRT85) root sheath differentiation, but not hair shaft differentiation. As in the HF, differentiation-specific keratins in BCC keratinocytes correlated with a reduced proliferative index and regulatory pathway activation despite the oncogenic drive towards tumour growth. Our findings show the close correlation between HF and BCC keratinocyte differentiation. CONCLUSION:This work has defined the differentiation pattern within BCCs, enabling development of targeted therapies that promote differentiation and result in BCC cancer stem cell exhaustion.

摘要

背景: 人基底细胞癌 (BCC) 癌症干细胞和细胞层次的鉴定固有地意味着分化的存在。通过常规组织学分析,BCC显示肿瘤结节出现相对均匀。 目的: 由于BCCs起源于毛囊 (HF) 角质形成细胞,我们试图定义HF分化的模式。 方法: 使用微阵列芯片分析BCC、鳞状细胞癌 (SCC) 和正常皮肤组织。采用逆转录-PCR和免疫荧光显微镜分析单个角蛋白的表达、调控通路和增殖状态。 结果: BCC、SCC和正常毛发皮肤的微阵列分析发现,BCCs表达广泛的HF基因,包括HF特异性角蛋白。BCC表现出外 (KRT5,KRT514,KRT516,KRT517 和KRT519) 和内部 (KRT25,KRT27,KRT28,KRT32,KRT35,KRT71,KRT75 和KRT85) root护套分化,但不是毛干分化。与HF一样,BCC角质形成细胞中的分化特异性角蛋白与增殖指数降低和调控通路激活相关,尽管致癌驱动肿瘤生长。我们的发现显示了HF和BCC角质形成细胞分化之间的密切相关性。 结论: 这项工作定义了BCCs内的分化模式,能够开发促进分化并导致BCC癌干细胞衰竭的靶向治疗。

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影响因子:2.93
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DOI:10.1016/j.jaad.2019.04.067
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影响因子:0.96
发表时间:2020-01-01
DOI:10.1097/DAD.0000000000001459
作者列表:["Lang UE","Love NR","Cheung C","McCalmont TH","Kim J"]

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皮肤肿瘤方向

皮肤肿瘤是发生在皮肤的细胞增生性疾病,是一种常见病。发生于皮内或皮下组织的新生物,种类很多,临床上分良性肿瘤和恶性肿瘤。恶性肿瘤可以不断增殖,引起转移,威胁生命,称为皮肤癌。

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