Mesenchymal stem cells (MSC) take part to solid tumour-associated stroma and critically influence progression of malignancy. Our study represents a striking example of melanoma progression to a more malignant and resistant phenotype promoted by MSC and the possibility to contrast this diabolic liaison using CAIX inhibitors. In particular, we demonstrated that melanoma cells exposed to a MSC-conditioned medium switch to a more malignant phenotype, characterised by resistance to programmed cell death and endowed with an epithelial-to-mesenchymal transition and stem cell characteristics. These effects were reversed abrogating MSC CAIX activity using SLC-0111, a CAIX inhibitor. Moreover, the acquisition by melanoma cells of a Vemurafenib-resistant phenotype upon MSC-conditioned medium exposure was removed when MSC were treated with SLC-0111. Therefore, MSC may profoundly reprogramme melanoma cells towards a wide resistant phenotype through CAIX involvement, as the use of SLC-0111 is able to contrast the development of this highly risky adaptation for disease progression.

中文翻译：

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碳酸酐酶IX抑制剂SLC-0111作为新兴的药物，可抵抗间充质干细胞对黑色素瘤细胞的促生存作用。

间充质干细胞（MSC）参与实体瘤相关基质，并严重影响恶性肿瘤的进展。我们的研究代表了一个令人惊讶的例子，表明黑素瘤进展为由MSC促进的更具恶性和耐药性的表型，并且有可能使用CAIX抑制剂来对比这种代谢不良的联系。特别是，我们证明了暴露于MSC条件培养基的黑色素瘤细胞会转变为更具恶性的表型，其特征是对程序性细胞死亡具有抵抗力，并具有上皮-间充质转化和干细胞特性。使用CAIX抑制剂SLC-0111可以消除MSC CAIX活性，从而逆转这些作用。此外，当用SLC-0111处理MSC时，黑色素瘤细胞在MSC条件培养基暴露后获得了对Vemurafenib耐药的表型。因此，