期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 35, 期 1, 页码 1185-1193出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2020.1764549
关键词
SLC-0111; CAIX inhibitor; MSC; melanoma
资金
- Istituto Toscano Tumori (ITT) (Decreto Dirigenziale Regione Toscana) [5254]
- Ente Cassa di Risparmio di Firenze
- Universita degli Studi di Firenze
- Associazione Italiana per la Ricerca sul Cancro (AIRC fellowship for Italy)
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.
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