Leo Angela, Pranzini Erica, Pietrovito Laura, Pardella Elisa, Parri Matteo, Cirri Paolo, Bruno Gennaro, Calvani Maura, Peppicelli Silvia, Torre Eugenio, Sasaki Maiko, Yang Lily, Zhu Lei, Chiarugi Paola, Raugei Giovanni, Arbiser Jack L, Taddei Maria Letizia
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
Division of Pediatric Oncology/Hematology, Meyer University Children's Hospital, 50139 Florence, Italy.
Cancers (Basel). 2021 Jul 15;13(14):3551. doi: 10.3390/cancers13143551.
Metastatic melanoma is characterized by poor prognosis and a low free-survival rate. Thanks to their high plasticity, melanoma cells are able to migrate exploiting different cell motility strategies, such as the rounded/amoeboid-type motility and the elongated/mesenchymal-type motility. In particular, the amoeboid motility strongly contributes to the dissemination of highly invasive melanoma cells and no treatment targeting this process is currently available for clinical application. Here, we tested Claisened Hexafluoro as a novel inhibitor of the amoeboid motility. Reported data demonstrate that Claisened Hexafluoro specifically inhibits melanoma cells moving through amoeboid motility by deregulating mitochondrial activity and activating the AMPK signaling. Moreover, Claisened Hexafluoro is able to interfere with the adhesion abilities and the stemness features of melanoma cells, thus decreasing the in vivo metastatic process. This evidence may contribute to pave the way for future possible therapeutic applications of Claisened Hexafluoro to counteract metastatic melanoma dissemination.
转移性黑色素瘤的特点是预后不良和无进展生存率低。由于黑色素瘤细胞具有高度可塑性，它们能够利用不同的细胞运动策略进行迁移，如圆形/阿米巴样运动和细长/间充质样运动。特别是，阿米巴样运动对高侵袭性黑色素瘤细胞的扩散有很大贡献，目前尚无针对该过程的治疗方法可用于临床应用。在这里，我们测试了克莱森六氟化物作为一种新型的阿米巴样运动抑制剂。报告的数据表明，克莱森六氟化物通过调节线粒体活性和激活AMPK信号通路，特异性地抑制通过阿米巴样运动迁移的黑色素瘤细胞。此外，克莱森六氟化物能够干扰黑色素瘤细胞的黏附能力和干性特征，从而减少体内转移过程。这一证据可能有助于为未来克莱森六氟化物对抗转移性黑色素瘤扩散的可能治疗应用铺平道路。
