Molecular Profiling of Keratinocyte Skin Tumors Links Staphylococcus aureus Overabundance and Increased Human β-Defensin-2 Expression to Growth Promotion of Squamous Cell Carcinoma

角质形成细胞皮肤肿瘤的分子分析表明金黄色葡萄球菌过多和人类 β-防御素-2 表达增加与鳞状细胞癌的生长促进有关

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作者:Nandhitha Madhusudhan, Manuela R Pausan, Bettina Halwachs, Marija Durdević, Markus Windisch, Jan Kehrmann, VijayKumar Patra, Peter Wolf, Petra Boukamp, Christine Moissl-Eichinger, Lorenzo Cerroni, Jürgen C Becker, Gregor Gorkiewicz

Abstract

The skin microbiota plays a prominent role in health and disease; however, its contribution to skin tumorigenesis is not well understood. We comparatively assessed the microbial community compositions from excision specimens of the main human non-melanoma skin cancers, actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Keratinocyte skin tumors are characterized by significantly different microbial community compositions, wherein AK and SCC are more similar to each other than to BCC. Notably, in SCC, which represents the advanced tumor entity and frequently develops from AK, overabundance of Staphylococcus aureus, a known skin pathogen, was noted. Moreover, S. aureus overabundance was significantly associated with increased human β-defensin-2 (hBD-2) expression in SCC. By challenging human SCC cell lines with S. aureus, a specific induction of hBD-2 expression and increased tumor cell growth was seen. Increased proliferation was also induced by directly challenging SCC cells with hBD-2. Together, our data indicate that a changed microbial community composition in SCC, specified by S. aureus overabundance, might promote tumor cell growth via modulation of hBD-2 expression.

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