文章：

着色性干皮病C型原代皮肤成纤维细胞在无基因毒性应激条件下过表达肝细胞生长因子并促进鳞状细胞癌侵袭

Xeroderma Pigmentosum Type C Primary Skin Fibroblasts Overexpress HGF and Promote Squamous Cell Carcinoma Invasion in the Absence of Genotoxic Stress

原文发布日期：26 September 2024

DOI: 10.3390/cancers16193277

类型: Article

开放获取: 是

英文摘要：

Xeroderma pigmentosum (XP) is a very rare recessive disease caused by the incapacity to resolve ultraviolet-induced DNA lesions through Nucleotide Excision Repair (NER). Most XP patients suffer from aggressive skin carcinoma and melanoma at a very early age (<8). Our previous results showed that primary XP fibroblasts isolated from healthy (non-photo-exposed) skin negatively impact the extracellular matrix and fail to activate the innate immune system. Here, we show for the first time that XP-C fibroblasts also play a major role in cancer cell invasion ex vivo and in vivo through the overexpression of Hepatocyte Growth Factor/Scatter Factor (HGF/SF) in the absence of genotoxic attacks. The use of inhibitors of the activation of the HGF/SF pathway counteracted the effects of XP fibroblasts on the growth of cancer cells, suggesting new perspectives in the care of XP patients.

摘要翻译： 

着色性干皮病（XP）是一种极为罕见的隐性遗传疾病，其病因在于患者无法通过核苷酸切除修复（NER）机制有效清除紫外线诱导的DNA损伤。多数XP患者在幼年时期（<8岁）即罹患侵袭性皮肤癌和黑色素瘤。我们前期的研究结果表明，从健康（非光暴露）皮肤分离的原代XP成纤维细胞会对细胞外基质产生负面影响，且无法激活先天免疫系统。本研究首次揭示，即使在无基因毒性攻击的情况下，XP-C型成纤维细胞仍能通过过度表达肝细胞生长因子/分散因子（HGF/SF），在离体及体内实验中显著促进癌细胞侵袭。通过使用HGF/SF通路激活抑制剂，可有效抵消XP成纤维细胞对癌细胞生长的促进作用，这为XP患者的临床治疗提供了新的思路。

原文链接：

Xeroderma Pigmentosum Type C Primary Skin Fibroblasts Overexpress HGF and Promote Squamous Cell Carcinoma Invasion in the Absence of Genotoxic Stress