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.
Highlights
Keratinocyte skin tumors are represented by two main entities, cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), which account for more than 90% of all skin malignancies with suggested 2–3 million global cases per year [1,2,3]
Antimicrobial peptides (AMPs), innate immune factors produced by epithelia and immune cells, are of special interest in this context, since they are induced in response to specific microbes and are implicated in tumorigenesis, since they affect tumor cell growth and migration—both are features associated with tumor progression [13,14]
Actinic keratosis (AK) and SCCs are often covered with abundant lamellar keratin on the lesional surface, which is a less pronounced feature in BCC (Figure S1A–F)
Summary
Keratinocyte skin tumors are represented by two main entities, cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), which account for more than 90% of all skin malignancies with suggested 2–3 million global cases per year [1,2,3]. Actinic keratosis (AK) is a premalignant lesion typically developing on photo-damaged skin. It can progress into SCC, but it can regress or remain stable over a long time without getting malignant. The microbial habitat is changed which might lead to an altered microbial colonization potentially favoring pro-tumorigenic microbes, which in turn could perpetuate tumorigenesis. Such an example was recently shown in colorectal carcinogenesis, wherein overexpression of a specific bacterial lectin (Gal-GalNAc) on the neoplastic colon epithelium leads to selective enrichment of tumor-driving Fusobacterium nucleatum [9]. Antimicrobial peptides (AMPs), innate immune factors produced by epithelia and immune cells, are of special interest in this context, since they are induced in response to specific microbes and are implicated in tumorigenesis, since they affect tumor cell growth and migration—both are features associated with tumor progression [13,14]
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