Accumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis

Background: Previous studies in mice indicated that Paneth cells and c-Kit-positive goblet cells represent the stem cell niche of the small intestine and colon, respectively, partly by supporting Wnt and Notch activation. Whether these cell populations play a similar role in human intestinal cancer...

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Autores principales:	Erika López-Arribillaga, Bing Yan, Teresa Lobo-Jarne, Yolanda Guillén, Silvia Menéndez, Montserrat Andreu, Anna Bigas, Mar Iglesias, Lluís Espinosa
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	colorectal cancer adenomas stem cell niche Paneth cells Wnt Notch Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a2b2abc47bf94a33859ea7afe20bbba6
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spelling	oai:doaj.org-article:a2b2abc47bf94a33859ea7afe20bbba62021-11-25T17:09:06ZAccumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis10.3390/cells101129282073-4409https://doaj.org/article/a2b2abc47bf94a33859ea7afe20bbba62021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2928https://doaj.org/toc/2073-4409Background: Previous studies in mice indicated that Paneth cells and c-Kit-positive goblet cells represent the stem cell niche of the small intestine and colon, respectively, partly by supporting Wnt and Notch activation. Whether these cell populations play a similar role in human intestinal cancer remains unexplored. Methods: We performed histopathological evaluation and immunohistochemical analysis of early colorectal adenomas and carcinoma adenoma from patients at the Hospital del Mar in Barcelona. We then determined the possible correlation between the different parameters analyzed and with patient outcomes. Results: Paneth cells accumulate in a subset of human colorectal adenomas directly associated with Notch and Wnt/β-catenin activation. Adenoma areas containing Paneth cells display increased vessel density in the lamina propria and higher levels of the stem cell marker EphB2. In an in-house cohort of 200 colorectal adenoma samples, we also observed a significant correlation between the presence of Paneth cells and Wnt activation. Kaplan–Meier analysis indicated that early adenoma patients carrying Paneth cell-positive tumors display reduced disease-free survival compared with patients with Paneth cell-free lesions. Conclusions: Our results indicate that Paneth cells contribute to the initial steps of cancer progression by providing the stem cell niche to adenoma cells, which could be therapeutically exploited.Erika López-ArribillagaBing YanTeresa Lobo-JarneYolanda GuillénSilvia MenéndezMontserrat AndreuAnna BigasMar IglesiasLluís EspinosaMDPI AGarticlecolorectal canceradenomasstem cell nichePaneth cellsWntNotchBiology (General)QH301-705.5ENCells, Vol 10, Iss 2928, p 2928 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer adenomas stem cell niche Paneth cells Wnt Notch Biology (General) QH301-705.5
spellingShingle	colorectal cancer adenomas stem cell niche Paneth cells Wnt Notch Biology (General) QH301-705.5 Erika López-Arribillaga Bing Yan Teresa Lobo-Jarne Yolanda Guillén Silvia Menéndez Montserrat Andreu Anna Bigas Mar Iglesias Lluís Espinosa Accumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis
description	Background: Previous studies in mice indicated that Paneth cells and c-Kit-positive goblet cells represent the stem cell niche of the small intestine and colon, respectively, partly by supporting Wnt and Notch activation. Whether these cell populations play a similar role in human intestinal cancer remains unexplored. Methods: We performed histopathological evaluation and immunohistochemical analysis of early colorectal adenomas and carcinoma adenoma from patients at the Hospital del Mar in Barcelona. We then determined the possible correlation between the different parameters analyzed and with patient outcomes. Results: Paneth cells accumulate in a subset of human colorectal adenomas directly associated with Notch and Wnt/β-catenin activation. Adenoma areas containing Paneth cells display increased vessel density in the lamina propria and higher levels of the stem cell marker EphB2. In an in-house cohort of 200 colorectal adenoma samples, we also observed a significant correlation between the presence of Paneth cells and Wnt activation. Kaplan–Meier analysis indicated that early adenoma patients carrying Paneth cell-positive tumors display reduced disease-free survival compared with patients with Paneth cell-free lesions. Conclusions: Our results indicate that Paneth cells contribute to the initial steps of cancer progression by providing the stem cell niche to adenoma cells, which could be therapeutically exploited.
format	article
author	Erika López-Arribillaga Bing Yan Teresa Lobo-Jarne Yolanda Guillén Silvia Menéndez Montserrat Andreu Anna Bigas Mar Iglesias Lluís Espinosa
author_facet	Erika López-Arribillaga Bing Yan Teresa Lobo-Jarne Yolanda Guillén Silvia Menéndez Montserrat Andreu Anna Bigas Mar Iglesias Lluís Espinosa
author_sort	Erika López-Arribillaga
title	Accumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis
title_short	Accumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis
title_full	Accumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis
title_fullStr	Accumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis
title_full_unstemmed	Accumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis
title_sort	accumulation of paneth cells in early colorectal adenomas is associated with beta-catenin signaling and poor patient prognosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a2b2abc47bf94a33859ea7afe20bbba6
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Accumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis

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