The antimicrobial peptide human cationic antimicrobial protein-18/cathelicidin LL-37 as a putative growth factor for malignant melanoma

Abstract

BACKGROUND: Recent evidence suggests cathelicidin LL-37 to be a growth factor for various human cancers such as lung cancer, ovarian cancer and breast cancer. However, the effect of LL-37 against malignant skin cancer has not been reported.

OBJECTIVES: To investigate whether the human cathelicidin LL-37 is involved in the carcinogenesis of various skin tumours.

METHODS: Human cationic antimicrobial protein-18 (hCAP-18)/LL-37 production in several cell lines including HaCaT, a chronic myelogenous leukaemia (CML) cell line and various melanoma cell lines was examined using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Immunohistochemical analysis of melanoma, nonmelanoma skin cancer and precancerous and benign skin lesions was performed. After adding LL-37 to a melanoma cell line, tumour cell proliferation, migration and invasion were investigated.

RESULTS: Human malignant melanoma cell lines overexpressed hCAP-18/LL-37 mRNA and peptide compared with HaCaT and CML cell lines. Immunohistochemistry showed that the peptide was strongly expressed in malignant melanoma and moderately expressed in squamous cell carcinoma, whereas basal cell carcinoma, precancerous lesions and seborrhoeic keratosis showed no or weak expression. LL-37 also stimulated melanoma cell proliferation, migration and invasion in vitro.

CONCLUSIONS: Cathelicidin LL-37 was primarily expressed in human malignant skin cancer. LL-37 promoted melanoma cell proliferation, migration and invasion in vitro. We report that an increase in the level of LL-37 is associated with malignant skin tumours such as malignant melanoma. These results highlight the importance of LL-37 in the malignant tendency of skin tumours.