The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness

Detalhes bibliográficos
Autor(a) principal: Pinto, F
Data de Publicação: 2021
Outros Autores: Santos-Ferreira, L, Pinto, MT, Gomes, C, Reis, CA
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/10216/152429
Resumo: Biglycan (BGN gene), an extracellular proteoglycan, has been described to be associated with cancer aggressiveness. The purpose of this study was to clarify the clinical value of biglycan as a biomarker in multiple independent GC cohorts and determine the in vitro and in vivo role of biglycan in GC malignant features. We found that BGN is commonly over-expressed in all analyzed cohorts, being associated with disease relapse and poor prognosis in patients with advanced stages of disease. In vitro and in vivo experiments demonstrated that biglycan knock-out GC cells display major phenotypic changes with a lower cell survival, migration, and angiogenic potential when compared with biglycan expressing cells. Biglycan KO GC cells present increased levels of PARP1 and caspase-3 cleavage and a decreased expression of mesenchymal markers. Importantly, biglycan deficient GC cells that were supplemented with exogenous biglycan were able to restore biological features, such as survival, clonogenic and migratory capacities. Our in vitro and in vivo findings were validated in human GC samples, where BGN expression was associated with several oncogenic gene signatures that were associated with apoptosis, cell migration, invasion, and angiogenesis. This study provided new insights on biglycan role in GC that should be taken in consideration as a key cellular regulator with major impact in tumor progression and patients’ clinical outcome.
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spelling The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressivenessBiglycanCancer aggressivenessGastric cancerPrognostic biomarkerSmall leucine-rich proteoglycanBiglycan (BGN gene), an extracellular proteoglycan, has been described to be associated with cancer aggressiveness. The purpose of this study was to clarify the clinical value of biglycan as a biomarker in multiple independent GC cohorts and determine the in vitro and in vivo role of biglycan in GC malignant features. We found that BGN is commonly over-expressed in all analyzed cohorts, being associated with disease relapse and poor prognosis in patients with advanced stages of disease. In vitro and in vivo experiments demonstrated that biglycan knock-out GC cells display major phenotypic changes with a lower cell survival, migration, and angiogenic potential when compared with biglycan expressing cells. Biglycan KO GC cells present increased levels of PARP1 and caspase-3 cleavage and a decreased expression of mesenchymal markers. Importantly, biglycan deficient GC cells that were supplemented with exogenous biglycan were able to restore biological features, such as survival, clonogenic and migratory capacities. Our in vitro and in vivo findings were validated in human GC samples, where BGN expression was associated with several oncogenic gene signatures that were associated with apoptosis, cell migration, invasion, and angiogenesis. This study provided new insights on biglycan role in GC that should be taken in consideration as a key cellular regulator with major impact in tumor progression and patients’ clinical outcome.MDPI20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/152429eng2072-669410.3390/cancers13061330Pinto, FSantos-Ferreira, LPinto, MTGomes, CReis, CAinfo: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:RCAAP2023-11-29T13:01:26Zoai:repositorio-aberto.up.pt:10216/152429Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T23:31:57.861390Repositório 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 The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness
title The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness
spellingShingle The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness
Pinto, F
Biglycan
Cancer aggressiveness
Gastric cancer
Prognostic biomarker
Small leucine-rich proteoglycan
title_short The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness
title_full The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness
title_fullStr The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness
title_full_unstemmed The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness
title_sort The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness
author Pinto, F
author_facet Pinto, F
Santos-Ferreira, L
Pinto, MT
Gomes, C
Reis, CA
author_role author
author2 Santos-Ferreira, L
Pinto, MT
Gomes, C
Reis, CA
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Pinto, F
Santos-Ferreira, L
Pinto, MT
Gomes, C
Reis, CA
dc.subject.por.fl_str_mv Biglycan
Cancer aggressiveness
Gastric cancer
Prognostic biomarker
Small leucine-rich proteoglycan
topic Biglycan
Cancer aggressiveness
Gastric cancer
Prognostic biomarker
Small leucine-rich proteoglycan
description Biglycan (BGN gene), an extracellular proteoglycan, has been described to be associated with cancer aggressiveness. The purpose of this study was to clarify the clinical value of biglycan as a biomarker in multiple independent GC cohorts and determine the in vitro and in vivo role of biglycan in GC malignant features. We found that BGN is commonly over-expressed in all analyzed cohorts, being associated with disease relapse and poor prognosis in patients with advanced stages of disease. In vitro and in vivo experiments demonstrated that biglycan knock-out GC cells display major phenotypic changes with a lower cell survival, migration, and angiogenic potential when compared with biglycan expressing cells. Biglycan KO GC cells present increased levels of PARP1 and caspase-3 cleavage and a decreased expression of mesenchymal markers. Importantly, biglycan deficient GC cells that were supplemented with exogenous biglycan were able to restore biological features, such as survival, clonogenic and migratory capacities. Our in vitro and in vivo findings were validated in human GC samples, where BGN expression was associated with several oncogenic gene signatures that were associated with apoptosis, cell migration, invasion, and angiogenesis. This study provided new insights on biglycan role in GC that should be taken in consideration as a key cellular regulator with major impact in tumor progression and patients’ clinical outcome.
publishDate 2021
dc.date.none.fl_str_mv 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 https://hdl.handle.net/10216/152429
url https://hdl.handle.net/10216/152429
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2072-6694
10.3390/cancers13061330
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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
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)
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