Tanaka Yuka, Ito Takamichi, Nishio Kiichiro, Tanegashima Keiko, Nakahara Takeshi
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Exp Dermatol. 2025 Sep;34(9):e70164. doi: 10.1111/exd.70164.
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.
肢端黑色素瘤（AM）是皮肤黑色素瘤的一种罕见亚型，主要发生在肢端部位。由于其罕见性以及与其他常见类型黑色素瘤相比该亚型的独特特征，晚期AM的治疗仍然具有挑战性。因此，迫切需要开发针对AM的有效治疗方法。本研究旨在筛选和评估AM的潜在治疗靶点。通过DNA微阵列分析比较正常表皮黑素细胞和AM细胞系（SM2-1和MMG-1）发现，与正常黑素细胞相比，AM细胞系中约有500个基因高表达。其中，黑色素瘤细胞粘附分子（MCAM）被选作进一步分析，结果发现与黑素细胞和角质形成细胞相比，MCAM在AM细胞系中显著高表达。敲低MCAM可显著抑制AM细胞系的增殖，同时细胞周期蛋白D1和BCL2的表达降低。进一步评估了靶向MCAM的抗体-药物偶联物的细胞毒性，结果显示其显著降低了AM细胞系的活力。总之，MCAM在AM细胞系中高表达，并可能通过调节细胞周期蛋白D1和BCL2的表达影响其增殖。这些发现凸显了MCAM作为AM治疗靶点的潜力。
