Abstract
LL-37, the active product of human cathelicidin antimicrobial peptide (CAMP) has a broad spectrum of antibacterial activity. LL-37 also has important physiological functions in immune regulation, angiogenesis and in modulating apoptosis. The roles of LL-37 in oral squamous cell carcinoma (OSCC) are still not clear. The correlation between DNA methylation and human CAMP expression is also unknown. Here human CAMP/LL-37 expression was assessed by immunohistochemistry in normal and OSCC tissues. The results indicated that low expression of CAMP/LL-37 correlated with histological differentiation and lymph node metastasis and also promoted tumor progression. A cell-specific methylation pattern in the promoter region of human CAMP was detected. Treatment with 5-aza-2′-deoxycytidine, a DNA demethylation reagent can increase human CAMP expression in epithelial cancer cells. The reporter assay showed that unmethylated human CAMP promoter activity was significantly higher than methylated promoter activity. Taken together, these results suggested that human CAMP/LL-37 might act as a tumor-suppressor in OSCC and DNA methylation might play roles during carcinogenesis via directly downregulating human CAMP promoter activity.
Highlights
Keratinocytes are the first mucosal epithelial cells to provide barrier protection against both oral and ingested enteric pathogens [1]
These results suggested that human cathelicidin antimicrobial peptide (CAMP)/LL-37 might act as a tumor-suppressor in oral squamous cell carcinoma (OSCC) and DNA methylation might play roles during carcinogenesis via directly downregulating human CAMP promoter activity
The results showed that CAMP/LL-37 is strongly expressed in normal oral mucosa (Figure 1A)
Summary
Keratinocytes are the first mucosal epithelial cells to provide barrier protection against both oral and ingested enteric pathogens [1]. Antimicrobial peptides (AMPs) within keratinocytes appear to increase resistance to bacterial invasion [1, 2]. Human cationic antibacterial peptide (CAMP, called hCAP18) is the only cathelicidin in humans, and is primarily found in the secondary granules of neutrophils [3, 4]. The C-terminal end of this protein contains a 37-amino acid-long peptide (LL-37) with a broad-spectrum antibacterial activity [4, 5]. Besides its broad antimicrobial activity, LL-37 plays roles in stimulation and modulation of cytokine release from different immune cells [3, 4]. The roles of LL-37 in oral squamous cell carcinoma (OSCC) are not clear
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