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dc.contributor.authorPeris Torres, Carlos
dc.contributor.authorPlaza Calonge, María del Carmen
dc.contributor.authorLópez Domínguez, Raúl 
dc.contributor.authorDomínguez García, Silvia
dc.contributor.authorBarrientos Durán, Antonio
dc.contributor.authorCarmona Sáez, Pedro 
dc.contributor.authorRodríguez-Manzaneque, Juan Carlos
dc.date.accessioned2020-06-12T12:46:41Z
dc.date.available2020-06-12T12:46:41Z
dc.date.issued2020-03
dc.identifier.citationPeris-Torres, C., Plaza-Calonge, M. D. C., López-Domínguez, R., Domínguez-García, S., Barrientos-Durán, A., Carmona-Sáez, P., & Rodríguez-Manzaneque, J. C. (2020). Extracellular Protease ADAMTS1 Is Required at Early Stages of Human Uveal Melanoma Development by Inducing Stemness and Endothelial-Like Features on Tumor Cells. Cancers, 12(4), 801. [doi:10.3390/cancers12040801]es_ES
dc.identifier.urihttp://hdl.handle.net/10481/62453
dc.descriptionWe would like to thank members of JCRM’s laboratory and GENYO’s support units for helping with animal handling, technical assistance, and further discussion. The results published here are in part based upon data generated by the TCGA Research Network (www.cancer.gov/tcga). This manuscript will be part of CPT PhD Thesis belonging to the Doctorate Program on Biomedicine, UGR, Spain.es_ES
dc.description.abstractExtracellular matrix remodeling within the tumor microenvironment has been recognized as a relevant dynamic framework during tumor growth. However, research on proteases that trigger this remodeling keeps revealing a wide range of actions including both pro- and anti-tumorigenic. The extracellular protease ADAMTS1 exemplifies this dual role. In this work, we first confirmed a positive correlation of ADAMTS1 with endothelial-like phenotype of human melanoma cells together with the finding of associated signatures, including key genes such as endothelial CDH5. Using a CRISPR-Cas9 approach, we observed that the inhibition of ADAMTS1 in an aggressive uveal melanoma model compromised its endothelial-like properties, and more importantly, caused a robust blockade on the progression of tumor xenografts. Although vasculature emerged affected in ADAMTS1-deficient tumors, the most relevant action implied the downregulation of endothelial CDH5 in tumor cells, in association with stemness markers. Indeed, melanoma sphere assays also revealed a deficient commitment to form spheres in the absence of ADAMTS1, directly correlating with stemness markers and, remarkably, also with CDH5. Finally, taking advantage of advanced bioinformatics tools and available public data of uveal melanomas, we disclosed new prognosis factors, including endothelial elements and ADAMTS proteases. Our findings support the key role of ADAMTS proteases for uveal melanoma development since earlier stages, modulating the complex crosstalk between extracellular matrix and the induction of stemness and endothelial-like features. To our knowledge, this is the first report that supports the development of therapeutic targets on the extracellular matrix to overcome uveal melanoma.es_ES
dc.description.sponsorshipThis research was supported by Ministerio de Economía y Competitividad and Instituto de Salud Carlos III from Spain, co-financed by FEDER (PI16/00345 to JCRM) and from Consejería de Salud de la Junta de Andalucía (OH-0028-2018, PE-0225-2018).es_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.rightsAtribución 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectADAMTSes_ES
dc.subjectCancer stem celles_ES
dc.subjectEndothelial-like phenotypees_ES
dc.subjectExtracellular-matrixes_ES
dc.subjectVasculogenic mimicryes_ES
dc.titleExtracellular Protease ADAMTS1 Is Required at Early Stages of Human Uveal Melanoma Development by Inducing Stemness and Endothelial-Like Features on Tumor Cellses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.identifier.doidoi:10.3390/cancers12040801


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Atribución 3.0 España
Except where otherwise noted, this item's license is described as Atribución 3.0 España