Fluctuating role of antimicrobial peptide hCAP18/LL-37 in oral tongue dysplasia and carcinoma

Abstract

Oral tongue squamous cell carcinoma (OTSCC), the most common cancer in the oral cavity, is aggressive and its incidence is increasing globally. Human host defense cationic antimicrobial peptide-18/antimicrobial peptide leucine-leucine-37 (hCAP18/LL-37) plays a complex role in various types of cancers. In the present study, we characterized the effects of exogenous LL-37 on three OTSCC cell lines and determined the expression of hCAP18/LL-37 in oral dysplastic and OTSCC patient samples. Our data revealed that LL-37, especially in high doses, mostly reduced the proliferation of OTSCC cells, but the effect was fluctuating. However, LL-37 stimulated the migration and invasion of OTSCC cells. The high dose of LL-37 also increased the amount of total epidermal growth factor receptor (EGFR) probably due to stabilization of the receptor to the plasma membrane. However, activation of EGFR downstream pathways was mostly decreased. Our immunohistochemical analysis showed that the hCAP18/LL-37 expression was higher in normal/mild dysplasia than in moderate/severe dysplasia and OTSCC. The hCAP18/LL-37 expression did not correlate with clinicopathological features or outcome of OTSCC patients. Our data suggest that LLc37 has a fluctuating effect on proliferation, migration and invasion of OTSCC cells, but it does not seem to play a role in the progression of OTSCC.