Investigation of the corticotropin-releasing hormone-proopiomelanocortin axis in various skin tumours

Abstract

BACKGROUND: Various types of external stress cause the skin and central neuroendocrine system to express corticotropin-releasing hormone (CRH)-proopiomelanocortin (POMC) axis-related hormones. However, the precise role of the CRH-POMC axis-related hormones in various skin tumours is unclear. OBJECTIVES: This study examined expression patterns of the CRH-POMC axis-related hormones in skin tumours. METHODS: The production of CRH, adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in various tumour cell lines including HaCaT and primary keratinocytes was examined using an enzyme-linked immunosorbent assay. Immunohistochemical analysis of the skin tumours was also performed. RESULTS: CRH, ACTH and alpha-MSH were strongly expressed in malignant skin tumour cell lines such as G-361 and DX-3 (both malignant melanoma, MM). However, normal and haematological malignancy cell lines did not express the CRH-POMC axis-related hormones. Immunohistochemical analysis of the skin tumours showed that MM (80%), squamous cell carcinoma (SCC, 70%) and basal cell carcinoma (BCC, 10%) had strong immunoreactivity (++/+++) for CRH. Strong ACTH and alpha-MSH expression was observed in MM (70% and 50%, respectively), SCC (80% and 60%, respectively) and BCC (70% and 50%, respectively). CONCLUSIONS: We report that an increase in the level of the CRH-POMC axis-related hormones is associated with malignant skin tumours such as MM. These results highlight the importance of the CRH-POMC axis-related hormones in the malignant tendency of skin tumours.