Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors

Extracellular adenosine triphosphate (ATP) conducts a complex dynamic system of broadly represented cell signaling. Ectonucleotidases are the enzymes with nucleotide hydrolytic ability that regulate ATP levels in physiological and pathological conditions, thus playing a key role in the so-called pur...

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Autores: Rodríguez-Martínez, Aitor, Torrejón-Escribano, Benjamín, Eritja, Núria, Dorca Arévalo, Jonatan, Gabaldón, Clara, Sévigny, Jean, Matias-Guiu, Xavier, 1958-, Martín Satué, Mireia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/217716
Acceso en línea:https://hdl.handle.net/2445/217716
Access Level:acceso abierto
Palabra clave:Càncer d'endometri
Cèl·lules epitelials
Citoquímica
Endometrial cancer
Epithelial cells
Cytochemistry
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spelling Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitorsRodríguez-Martínez, AitorTorrejón-Escribano, BenjamínEritja, NúriaDorca Arévalo, JonatanGabaldón, ClaraSévigny, JeanMatias-Guiu, Xavier, 1958-Martín Satué, MireiaCàncer d'endometriCèl·lules epitelialsCitoquímicaEndometrial cancerEpithelial cellsCytochemistryExtracellular adenosine triphosphate (ATP) conducts a complex dynamic system of broadly represented cell signaling. Ectonucleotidases are the enzymes with nucleotide hydrolytic ability that regulate ATP levels in physiological and pathological conditions, thus playing a key role in the so-called purinergic signaling. Altered ectonucleotidase expression has been reported in cancer, and the ectonucleoside triphosphate diphosphohydrolase (NTPDase) family of enzymes, with its best-known form NTPDase1 (CD39), is targeted in cancer immunotherapy. The tandem of enzymes CD39-CD73 is responsible for the generation of immuno-suppressive adenosine in the tumor microenvironment, and inhibition strategies are of great interest. Organoids have emerged as very convenient models for the study of tumors since they are three-dimensional cultures that retain many of the features of tissue. The present study aims to contribute to improving the methodology and the molecular tools needed for the study of ecto-nucleotidases in healthy and disease conditions. The study, performed in an endometrial cancer cell model, could be extended to other types of tumors and pathologies in which the purinergic system is involved. We generated organoids from endometrial cancer cells overexpressing NTPDase2 (CD39L1) and NTPDase3 (CD39L3) as fusion proteins with EGFP, and we performed functional assays by adapting in situ cytochemistry protocols. This allowed us to simultaneously detect enzyme activity and protein expression and to demonstrate that organoids can be used to test ectonucleotidase inhibitors—a result that can be used to develop new cancer treatment options.Sercrisma International2025202520242025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/217716Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.14670/HH-18-782Histology and Histopathology, 2024, vol. 39, p. 171-182https://doi.org/10.14670/HH-18-782cc by (c) Rodríguez-Martínez, Aitor et al., 2024https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2177162026-05-29T05:05:01Z
dc.title.none.fl_str_mv Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors
title Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors
spellingShingle Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors
Rodríguez-Martínez, Aitor
Càncer d'endometri
Cèl·lules epitelials
Citoquímica
Endometrial cancer
Epithelial cells
Cytochemistry
title_short Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors
title_full Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors
title_fullStr Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors
title_full_unstemmed Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors
title_sort Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors
dc.creator.none.fl_str_mv Rodríguez-Martínez, Aitor
Torrejón-Escribano, Benjamín
Eritja, Núria
Dorca Arévalo, Jonatan
Gabaldón, Clara
Sévigny, Jean
Matias-Guiu, Xavier, 1958-
Martín Satué, Mireia
author Rodríguez-Martínez, Aitor
author_facet Rodríguez-Martínez, Aitor
Torrejón-Escribano, Benjamín
Eritja, Núria
Dorca Arévalo, Jonatan
Gabaldón, Clara
Sévigny, Jean
Matias-Guiu, Xavier, 1958-
Martín Satué, Mireia
author_role author
author2 Torrejón-Escribano, Benjamín
Eritja, Núria
Dorca Arévalo, Jonatan
Gabaldón, Clara
Sévigny, Jean
Matias-Guiu, Xavier, 1958-
Martín Satué, Mireia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer d'endometri
Cèl·lules epitelials
Citoquímica
Endometrial cancer
Epithelial cells
Cytochemistry
topic Càncer d'endometri
Cèl·lules epitelials
Citoquímica
Endometrial cancer
Epithelial cells
Cytochemistry
description Extracellular adenosine triphosphate (ATP) conducts a complex dynamic system of broadly represented cell signaling. Ectonucleotidases are the enzymes with nucleotide hydrolytic ability that regulate ATP levels in physiological and pathological conditions, thus playing a key role in the so-called purinergic signaling. Altered ectonucleotidase expression has been reported in cancer, and the ectonucleoside triphosphate diphosphohydrolase (NTPDase) family of enzymes, with its best-known form NTPDase1 (CD39), is targeted in cancer immunotherapy. The tandem of enzymes CD39-CD73 is responsible for the generation of immuno-suppressive adenosine in the tumor microenvironment, and inhibition strategies are of great interest. Organoids have emerged as very convenient models for the study of tumors since they are three-dimensional cultures that retain many of the features of tissue. The present study aims to contribute to improving the methodology and the molecular tools needed for the study of ecto-nucleotidases in healthy and disease conditions. The study, performed in an endometrial cancer cell model, could be extended to other types of tumors and pathologies in which the purinergic system is involved. We generated organoids from endometrial cancer cells overexpressing NTPDase2 (CD39L1) and NTPDase3 (CD39L3) as fusion proteins with EGFP, and we performed functional assays by adapting in situ cytochemistry protocols. This allowed us to simultaneously detect enzyme activity and protein expression and to demonstrate that organoids can be used to test ectonucleotidase inhibitors—a result that can be used to develop new cancer treatment options.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/217716
url https://hdl.handle.net/2445/217716
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.14670/HH-18-782
Histology and Histopathology, 2024, vol. 39, p. 171-182
https://doi.org/10.14670/HH-18-782
dc.rights.none.fl_str_mv cc by (c) Rodríguez-Martínez, Aitor et al., 2024
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Rodríguez-Martínez, Aitor et al., 2024
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
application/pdf
dc.publisher.none.fl_str_mv Sercrisma International
publisher.none.fl_str_mv Sercrisma International
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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