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  2. The Carbonic Anhydrase IX inhibitor SLC-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells

The Carbonic Anhydrase IX inhibitor SLC-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells

  • J Enzyme Inhib Med Chem. 2020 Dec;35(1):1185-1193. doi: 10.1080/14756366.2020.1764549.
Silvia Peppicelli 1 Elena Andreucci 1 Jessica Ruzzolini 1 Francesca Bianchini 1 Chiara Nediani 1 Claudiu T Supuran 2 Lido Calorini 1 3
Affiliations

Affiliations

  • 1 Department of Clinical and Experimental Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, University of Florence, Florence, Italy.
  • 2 Department of NEUROFARBA, University of Florence, Florence, Italy.
  • 3 Center of Excellence for Research, Transfer and High Education, DenoTHE University of Florence, Florence, Italy.
Abstract

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.

Keywords

CAIX inhibitor; MSC; SLC-0111; melanoma.

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