Colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.

The cancer stem cell (CSC) concept proposes that cancer recurrence and metastasis are driven by CSCs. In this study, we investigated whether cells from colon adenocarcinoma (CA) with a CSC-like phenotype express renin-angiotensin system (RAS) components, and the effect of RAS inhibitors on CA-derive...

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Autores principales:	Matthew J Munro, Lifeng Peng, Susrutha K Wickremesekera, Swee T Tan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9f855c6e7f49498b8728b7c5a6dfbb3e
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spelling	oai:doaj.org-article:9f855c6e7f49498b8728b7c5a6dfbb3e2021-12-02T20:17:37ZColon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.1932-620310.1371/journal.pone.0256280https://doaj.org/article/9f855c6e7f49498b8728b7c5a6dfbb3e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256280https://doaj.org/toc/1932-6203The cancer stem cell (CSC) concept proposes that cancer recurrence and metastasis are driven by CSCs. In this study, we investigated whether cells from colon adenocarcinoma (CA) with a CSC-like phenotype express renin-angiotensin system (RAS) components, and the effect of RAS inhibitors on CA-derived primary cell lines. Expression of RAS components was interrogated using immunohistochemical and immunofluorescence staining in 6 low-grade CA (LGCA) and 6 high-grade CA (HGCA) tissue samples and patient-matched normal colon samples. Primary cell lines derived from 4 HGCA tissues were treated with RAS inhibitors to investigate their effect on cellular metabolism, tumorsphere formation and transcription of pluripotency genes. Immunohistochemical and immunofluorescence staining showed expression of AT2R, ACE2, PRR, and cathepsins B and D by cells expressing pluripotency markers. β-blockers and AT2R antagonists reduced cellular metabolism, pluripotency marker expression, and tumorsphere-forming capacity of CA-derived primary cell lines. This study suggests that the RAS is active in CSC-like cells in CA, and further investigation is warranted to determine whether RAS inhibition is a viable method of targeting CSCs.Matthew J MunroLifeng PengSusrutha K WickremesekeraSwee T TanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256280 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthew J Munro Lifeng Peng Susrutha K Wickremesekera Swee T Tan Colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.
description	The cancer stem cell (CSC) concept proposes that cancer recurrence and metastasis are driven by CSCs. In this study, we investigated whether cells from colon adenocarcinoma (CA) with a CSC-like phenotype express renin-angiotensin system (RAS) components, and the effect of RAS inhibitors on CA-derived primary cell lines. Expression of RAS components was interrogated using immunohistochemical and immunofluorescence staining in 6 low-grade CA (LGCA) and 6 high-grade CA (HGCA) tissue samples and patient-matched normal colon samples. Primary cell lines derived from 4 HGCA tissues were treated with RAS inhibitors to investigate their effect on cellular metabolism, tumorsphere formation and transcription of pluripotency genes. Immunohistochemical and immunofluorescence staining showed expression of AT2R, ACE2, PRR, and cathepsins B and D by cells expressing pluripotency markers. β-blockers and AT2R antagonists reduced cellular metabolism, pluripotency marker expression, and tumorsphere-forming capacity of CA-derived primary cell lines. This study suggests that the RAS is active in CSC-like cells in CA, and further investigation is warranted to determine whether RAS inhibition is a viable method of targeting CSCs.
format	article
author	Matthew J Munro Lifeng Peng Susrutha K Wickremesekera Swee T Tan
author_facet	Matthew J Munro Lifeng Peng Susrutha K Wickremesekera Swee T Tan
author_sort	Matthew J Munro
title	Colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.
title_short	Colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.
title_full	Colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.
title_fullStr	Colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.
title_full_unstemmed	Colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.
title_sort	colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9f855c6e7f49498b8728b7c5a6dfbb3e
work_keys_str_mv	AT matthewjmunro colonadenocarcinomaderivedcellspossessingstemcellfunctioncanbemodulatedusingreninangiotensinsysteminhibitors AT lifengpeng colonadenocarcinomaderivedcellspossessingstemcellfunctioncanbemodulatedusingreninangiotensinsysteminhibitors AT susruthakwickremesekera colonadenocarcinomaderivedcellspossessingstemcellfunctioncanbemodulatedusingreninangiotensinsysteminhibitors AT sweettan colonadenocarcinomaderivedcellspossessingstemcellfunctioncanbemodulatedusingreninangiotensinsysteminhibitors
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Colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.

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