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

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 liais...

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Autores principales: Peppicelli, Silvia, Andreucci, Elena, Ruzzolini, Jessica, Bianchini, Francesca, Nediani, Chiara, Supuran, Claudiu T., Calorini, Lido
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269050/
https://www.ncbi.nlm.nih.gov/pubmed/32396749
http://dx.doi.org/10.1080/14756366.2020.1764549
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author Peppicelli, Silvia
Andreucci, Elena
Ruzzolini, Jessica
Bianchini, Francesca
Nediani, Chiara
Supuran, Claudiu T.
Calorini, Lido
author_facet Peppicelli, Silvia
Andreucci, Elena
Ruzzolini, Jessica
Bianchini, Francesca
Nediani, Chiara
Supuran, Claudiu T.
Calorini, Lido
author_sort Peppicelli, Silvia
collection PubMed
description 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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spelling pubmed-72690502020-06-11 The Carbonic Anhydrase IX inhibitor SLC-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells Peppicelli, Silvia Andreucci, Elena Ruzzolini, Jessica Bianchini, Francesca Nediani, Chiara Supuran, Claudiu T. Calorini, Lido J Enzyme Inhib Med Chem Research Paper 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. Taylor & Francis 2020-05-12 /pmc/articles/PMC7269050/ /pubmed/32396749 http://dx.doi.org/10.1080/14756366.2020.1764549 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Peppicelli, Silvia
Andreucci, Elena
Ruzzolini, Jessica
Bianchini, Francesca
Nediani, Chiara
Supuran, Claudiu T.
Calorini, Lido
The Carbonic Anhydrase IX inhibitor SLC-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells
title The Carbonic Anhydrase IX inhibitor SLC-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells
title_full The Carbonic Anhydrase IX inhibitor SLC-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells
title_fullStr The Carbonic Anhydrase IX inhibitor SLC-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells
title_full_unstemmed The Carbonic Anhydrase IX inhibitor SLC-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells
title_short The Carbonic Anhydrase IX inhibitor SLC-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells
title_sort carbonic anhydrase ix inhibitor slc-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269050/
https://www.ncbi.nlm.nih.gov/pubmed/32396749
http://dx.doi.org/10.1080/14756366.2020.1764549
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