Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , |
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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7160 |
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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 instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
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 |
repository.mail.fl_str_mv |
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1799134560866271232 |