Doxorubicin-sensitive and -resistant colorectal cancer spheroid models

Detalhes bibliográficos
Autor(a) principal: Valente, Ruben
Data de Publicação: 2023
Outros Autores: Cordeiro, Sandra, Luz, André, Rodrigues, Catarina Roma, Baptista, Pedro V., Fernandes, Alexandra R.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/164612
Resumo: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financed by national funds from FCT–Fundação para a Ciência e a Tecnologia, I.P./MCTES through the projects PTDC/QUIQIN/0146/2020. Publisher Copyright: Copyright © 2023 Valente, Cordeiro, Luz, Melo, Rodrigues, Baptista and Fernandes.
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spelling Doxorubicin-sensitive and -resistant colorectal cancer spheroid modelsassessing tumor microenvironment features for therapeutic modulationchemoresistancecolorectal cancerdoxorubicinextracellular vesiclesheterotypic spheroid modelstumor microenvironmentDevelopmental BiologyCell BiologySDG 3 - Good Health and Well-beingThe author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financed by national funds from FCT–Fundação para a Ciência e a Tecnologia, I.P./MCTES through the projects PTDC/QUIQIN/0146/2020. Publisher Copyright: Copyright © 2023 Valente, Cordeiro, Luz, Melo, Rodrigues, Baptista and Fernandes.Introduction: The research on tumor microenvironment (TME) has recently been gaining attention due to its important role in tumor growth, progression, and response to therapy. Because of this, the development of three-dimensional cancer models that mimic the interactions in the TME and the tumor structure and complexity is of great relevance to cancer research and drug development. Methods: This study aimed to characterize colorectal cancer spheroids overtime and assess how the susceptibility or resistance to doxorubicin (Dox) or the inclusion of fibroblasts in heterotypic spheroids influence and modulate their secretory activity, namely the release of extracellular vesicles (EVs), and the response to Dox-mediated chemotherapy. Different characteristics were assessed over time, namely spheroid growth, viability, presence of hypoxia, expression of hypoxia and inflammation-associated genes and proteins. Due to the importance of EVs in biomarker discovery with impact on early diagnostics, prognostics and response to treatment, proteomic profiling of the EVs released by the different 3D spheroid models was also assessed. Response to treatment was also monitored by assessing Dox internalization and its effects on the different 3D spheroid structures and on the cell viability. Results and Discussion: The results show that distinct features are affected by both Dox resistance and the presence of fibroblasts. Fibroblasts can stabilize spheroid models, through the modulation of their growth, viability, hypoxia and inflammation levels, as well as the expressions of its associated transcripts/proteins, and promotes alterations in the protein profile exhibit by EVs. Summarily, fibroblasts can increase cell-cell and cell-extracellular matrix interactions, making the heterotypic spheroids a great model to study TME and understand TME role in chemotherapies resistance. Dox resistance induction is shown to influence the internalization of Dox, especially in homotypic spheroids, and it is also shown to influence cell viability and consequently the chemoresistance of those spheroids when exposed to Dox. Taken together these results highlight the importance of finding and characterizing different 3D models resembling more closely the in vivo interactions of tumors with their microenvironment as well as modulating drug resistance.DCV - Departamento de Ciências da VidaUCIBIO - Applied Molecular Biosciences UnitRUNValente, RubenCordeiro, SandraLuz, AndréRodrigues, Catarina RomaBaptista, Pedro V.Fernandes, Alexandra R.2024-03-07T23:39:51Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article25http://hdl.handle.net/10362/164612eng2296-634XPURE: 81488670https://doi.org/10.3389/fcell.2023.1310397info: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:RCAAP2024-03-18T01:44:18Zoai:run.unl.pt:10362/164612Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T04:00:16.619983Repositório 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 Doxorubicin-sensitive and -resistant colorectal cancer spheroid models
assessing tumor microenvironment features for therapeutic modulation
title Doxorubicin-sensitive and -resistant colorectal cancer spheroid models
spellingShingle Doxorubicin-sensitive and -resistant colorectal cancer spheroid models
Valente, Ruben
chemoresistance
colorectal cancer
doxorubicin
extracellular vesicles
heterotypic spheroid models
tumor microenvironment
Developmental Biology
Cell Biology
SDG 3 - Good Health and Well-being
title_short Doxorubicin-sensitive and -resistant colorectal cancer spheroid models
title_full Doxorubicin-sensitive and -resistant colorectal cancer spheroid models
title_fullStr Doxorubicin-sensitive and -resistant colorectal cancer spheroid models
title_full_unstemmed Doxorubicin-sensitive and -resistant colorectal cancer spheroid models
title_sort Doxorubicin-sensitive and -resistant colorectal cancer spheroid models
author Valente, Ruben
author_facet Valente, Ruben
Cordeiro, Sandra
Luz, André
Rodrigues, Catarina Roma
Baptista, Pedro V.
Fernandes, Alexandra R.
author_role author
author2 Cordeiro, Sandra
Luz, André
Rodrigues, Catarina Roma
Baptista, Pedro V.
Fernandes, Alexandra R.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv DCV - Departamento de Ciências da Vida
UCIBIO - Applied Molecular Biosciences Unit
RUN
dc.contributor.author.fl_str_mv Valente, Ruben
Cordeiro, Sandra
Luz, André
Rodrigues, Catarina Roma
Baptista, Pedro V.
Fernandes, Alexandra R.
dc.subject.por.fl_str_mv chemoresistance
colorectal cancer
doxorubicin
extracellular vesicles
heterotypic spheroid models
tumor microenvironment
Developmental Biology
Cell Biology
SDG 3 - Good Health and Well-being
topic chemoresistance
colorectal cancer
doxorubicin
extracellular vesicles
heterotypic spheroid models
tumor microenvironment
Developmental Biology
Cell Biology
SDG 3 - Good Health and Well-being
description The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financed by national funds from FCT–Fundação para a Ciência e a Tecnologia, I.P./MCTES through the projects PTDC/QUIQIN/0146/2020. Publisher Copyright: Copyright © 2023 Valente, Cordeiro, Luz, Melo, Rodrigues, Baptista and Fernandes.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-01T00:00:00Z
2024-03-07T23:39:51Z
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/10362/164612
url http://hdl.handle.net/10362/164612
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2296-634X
PURE: 81488670
https://doi.org/10.3389/fcell.2023.1310397
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 25
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
instname_str 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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