Targeting Melanoma Cell Adhesion Molecule as a Novel Therapeutic Approach for Acral Melanoma

Acral melanoma (AM) is a rare subtype of cutaneous melanoma mainly found in acral locations. The treatment of advanced AM remains challenging due to its rarity and the distinct features of this subtype compared with the other common types of melanomas. There is thus an urgent need to develop effective therapeutic approaches for AM. This study was established to screen and evaluate potential therapeutic targets for AM. DNA microarray analysis comparing normal epidermal melanocytes and AM cell lines (SM2-1 and MMG-1) showed that approximately 500 genes were highly expressed in the AM cell lines compared with the levels in normal melanocytes. Among them, melanoma cell adhesion molecule (MCAM) was selected for further analyses and was found to be significantly highly expressed in AM cell lines compared with the levels in melanocytes and keratinocytes. Knockdown of MCAM significantly inhibited the proliferation of AM cell lines with decreased expression of cyclin D1 and BCL2. The cytotoxicity of MCAM-targeted antibody-drug conjugate was further evaluated and it significantly decreased the viability of AM cell lines. In conclusion, MCAM is highly expressed in AM cell lines and affects their proliferation, likely through modulating the expression of cyclin D1 and BCL2. These findings highlight the potential of MCAM as a therapeutic target of AM.