Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures

Detalhes bibliográficos
Autor(a) principal: da Mata, Sara
Data de Publicação: 2021
Outros Autores: Franchi-Mendes, Teresa, Abreu, Sofia, Filipe, Bruno, Morgado, Sónia, Mesquita, Marta, Albuquerque, Cristina, Fonseca, Ricardo, Santo, Vítor E., Boghaert, Erwin R., Rosa, Isadora, Brito, Catarina
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/49661
Resumo: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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spelling Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term culturesColorectal cancerPatient-derived explantsTranslational models© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Colorectal cancer (CRC) is one of the most common cancers worldwide. Although short-term cultures of tumour sections and xenotransplants have been used to determine drug efficacy, the results frequently fail to confer clinically useful information. Biomarker discovery has changed the paradigm for advanced CRC, though the presence of a biomarker does not necessarily translate into therapeutic success. To improve clinical outcomes, translational models predictive of drug response are needed. We describe a simple method for the fast establishment of CRC patient-derived explant (CRC-PDE) cultures from different carcinogenesis pathways, employing agitation-based platforms. A total of 26 CRC-PDE were established and a subset was evaluated for viability (n = 23), morphology and genetic key alterations (n = 21). CRC-PDE retained partial tumor glandular architecture and microenvironment features were partially lost over 4 weeks of culture. Key proteins (p53 and Mismatch repair) and oncogenic driver mutations of the original tumours were sustained throughout the culture. Drug challenge (n = 5) revealed differential drug response from distinct CRC-PDE cases. These findings suggest an adequate representation of the original tumour and highlight the importance of detailed model characterisation. The preservation of key aspects of the CRC microenvironment and genetics supports CRC-PDE potential applicability in pre- and co-clinical settings, as long as temporal dynamics are considered.This research was supported by AbbVie and by iNOVA4Health—UIDB/04462/2020, a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds. TFM and SA were recipients of individual PhD fellowships funded by FCT (PD/BD/128377/2017 and PD/BD/105768/2014, respectively). CB acknowledges the support from “The Discoveries Centre for Regenerative and Precision Medicine” (European Commission Horizon 2020 Research and Innovation programme, under the Grant Agreement number 739572).MDPIRepositório da Universidade de Lisboada Mata, SaraFranchi-Mendes, TeresaAbreu, SofiaFilipe, BrunoMorgado, SóniaMesquita, MartaAlbuquerque, CristinaFonseca, RicardoSanto, Vítor E.Boghaert, Erwin R.Rosa, IsadoraBrito, Catarina2021-09-28T14:28:21Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49661engCancers (Basel). 2021 Sep 19;13(18):469510.3390/cancers131846952072-6694info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:53:37Zoai:repositorio.ul.pt:10451/49661Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:18.122186Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures
title Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures
spellingShingle Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures
da Mata, Sara
Colorectal cancer
Patient-derived explants
Translational models
title_short Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures
title_full Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures
title_fullStr Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures
title_full_unstemmed Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures
title_sort Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures
author da Mata, Sara
author_facet da Mata, Sara
Franchi-Mendes, Teresa
Abreu, Sofia
Filipe, Bruno
Morgado, Sónia
Mesquita, Marta
Albuquerque, Cristina
Fonseca, Ricardo
Santo, Vítor E.
Boghaert, Erwin R.
Rosa, Isadora
Brito, Catarina
author_role author
author2 Franchi-Mendes, Teresa
Abreu, Sofia
Filipe, Bruno
Morgado, Sónia
Mesquita, Marta
Albuquerque, Cristina
Fonseca, Ricardo
Santo, Vítor E.
Boghaert, Erwin R.
Rosa, Isadora
Brito, Catarina
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv da Mata, Sara
Franchi-Mendes, Teresa
Abreu, Sofia
Filipe, Bruno
Morgado, Sónia
Mesquita, Marta
Albuquerque, Cristina
Fonseca, Ricardo
Santo, Vítor E.
Boghaert, Erwin R.
Rosa, Isadora
Brito, Catarina
dc.subject.por.fl_str_mv Colorectal cancer
Patient-derived explants
Translational models
topic Colorectal cancer
Patient-derived explants
Translational models
description © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
publishDate 2021
dc.date.none.fl_str_mv 2021-09-28T14:28:21Z
2021
2021-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/49661
url http://hdl.handle.net/10451/49661
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Cancers (Basel). 2021 Sep 19;13(18):4695
10.3390/cancers13184695
2072-6694
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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