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

Summary 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 cathel...

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Bibliographic Details
Published in:	British journal of dermatology (1951) 2010-11, Vol.163 (5), p.959-967
Main Authors:	Kim, J.E., Kim, H.J., Choi, J.M., Lee, K.H., Kim, T.Y., Cho, B.K., Jung, J.Y., Chung, K.Y., Cho, D., Park, H.J.
Format:	Article
Language:	eng
Subjects:	Adult Aged Aged, 80 and over Antimicrobial agents Antimicrobial Cationic Peptides - metabolism antimicrobial peptide Antimicrobial peptides Basal cells Benign Biological and medical sciences Breast cancer Carcinogenesis cathelicidins Cell Line, Tumor - metabolism Cell migration Cell Movement - physiology Cell Proliferation Chronic myeloid leukemia Dermatology Enzyme-Linked Immunosorbent Assay Female Growth factors Humans Immunohistochemistry Keratosis Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology LL-37 Lung cancer Male malignant skin cancer Medical sciences Melanoma Melanoma - metabolism Melanoma - pathology Middle Aged Neoplasm Invasiveness - pathology Neoplasm Proteins - metabolism Ovarian cancer Precancerous Conditions - metabolism RNA, Messenger - metabolism Skin cancer Skin diseases Skin Neoplasms - metabolism Skin Neoplasms - pathology skin tumours squamous cell carcinoma Tumor cell lines Tumors of the skin and soft tissue. Premalignant lesions tumour progression
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Summary:	Summary 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.
ISSN:	0007-0963 1365-2133