Stromal microenvironment in type VII collagen-deficient skin: The ground for squamous cell carcinoma development
Stromal microenvironment in type VII collagen-deficient skin: The ground for squamous cell carcinoma development
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DOI：
10.1016/j.matbio.2017.01.002
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发表时间：
2017-11-01
期刊：
影响因子：
6.9
通讯作者：
Castiglia, Daniele
中科院分区：
文献类型：
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作者：
Guerra, Liliana;Odorisio, Teresa;Castiglia, Daniele
隐性营养不良性大疱性表皮松解症 (RDEB) 是一种皮肤脆性疾病，由影响 VII 型胶原蛋白 (C7) 功能和/或数量的突变引起，而 VII 型胶原蛋白是锚定原纤维的主要成分。 RDEB 的特点是持续不断的起泡和慢性伤口，导致组织纤维化和疤痕。几乎所有患有严重 RDEB 的患者都会发展为高度转移的鳞状细胞癌 (SCC)，这是死亡的主要原因。来自小鼠 RDEB 模型和人类 RDEB 细胞的积累证据表明，C7 的缺乏也会直接改变伤口愈合过程。不愈合的 RDEB 伤口的特点是炎症增加、转化生长因子-β 1 (TGF-β 1) 水平和活性高，并且肌成纤维细胞大量繁殖，导致纤维生成和基质硬度增强。这些变化使得 RDEB 基质成为一个容易引发癌症的微环境，其中发现了具有癌症相关成纤维细胞特征的细胞。在这里，我们讨论关于 RDEB 微环境改变的最新知识，强调预防和/或延迟纤维化和鳞状细胞癌发展的可能治疗靶点。 (C) 2017 Elsevier B.V. 保留所有权利。
Recessive dystrophic epidermolysis bullosa (RDEB) is a skin fragility disease caused by mutations that affect the function and/or the amount of type VII collagen (C7), the major component of anchoring fibrils. Hallmarks of RDEB are unremitting blistering and chronic wounds leading to tissue fibrosis and scarring. Nearly all patients with severe RDEB develop highly metastatic squamous cell carcinomas (SCC) which are the main cause of death. Accumulating evidence from a murine RDEB model and human RDEB cells demonstrates that lack of C7 also directly alters the wound healing process. Non-healing RDEB wounds are characterized by increased inflammation, high transforming growth factor-beta 1 (TGF-beta 1)levels and activity, and are heavily populated by myofibroblasts responsible for enhanced fibrogenesis and matrix stiffness. These changes make the RDEB stroma a microenvironment prone to cancer initiation, where cells with features of cancer associated fibroblasts are found. Here, we discuss recent knowledge on microenvironment alterations in RDEB, highlighting possible therapeutic targets to prevent and/or delay fibrosis and SCC development. (C) 2017 Elsevier B.V. All rights reserved.