Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis

BackgroundMacrophage extracellular traps (METs) and tumor-infiltrating macrophages contribute to the progression of several diseases. But the role of METs and tumor-infiltrating macrophages in colon cancer (CC) has not been illuminated. In this study, we aimed to clarify the prognostic value of METs...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tianli Chen, Yue Wang, Zhaodi Nan, Jie Wu, Ailu Li, Tingguo Zhang, Xun Qu, Chen Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	colon cancer macrophage extracellular traps (METs) prognosis PAD2 PAD2-IN-1 Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/19841d9db9994f3292dc8a4808be0318
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:19841d9db9994f3292dc8a4808be0318
record_format	dspace
spelling	oai:doaj.org-article:19841d9db9994f3292dc8a4808be03182021-12-01T22:02:11ZInteraction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis1664-322410.3389/fimmu.2021.779325https://doaj.org/article/19841d9db9994f3292dc8a4808be03182021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.779325/fullhttps://doaj.org/toc/1664-3224BackgroundMacrophage extracellular traps (METs) and tumor-infiltrating macrophages contribute to the progression of several diseases. But the role of METs and tumor-infiltrating macrophages in colon cancer (CC) has not been illuminated. In this study, we aimed to clarify the prognostic value of METs for CC patients and to explore the interaction between CC cells and METs in vitro and in vivo.MethodsA training cohort consisting of 116 patients and a validation cohort of 94 patients were enrolled in this study. Immunofluorescence (IF) staining was conducted to determine METs formation in CC patients. Cox regression was used to perform prognostic analysis and screen out the best prognostic model. A nomogram was established to predict 5-year overall survival (OS). The correlation between METs with clinicopathological features and inflammatory markers was analyzed. The formation of METs in vitro was detected by SYTOX® green and IF staining, and the effect of METs on CC cells was detected by transwell assays. PAD2-IN-1, a selective inhibitor of peptidylarginine deiminase 2 (PAD2), was introduced to destroy the crosstalk between CC cells and METs in vitro and in vivo.ResultsMETs levels were higher in CC tissues and were an independent prognostic factor for CC patients. The prognostic model consisting of age, tumors local invasion, lymph node metastasis and METs were confirmed to be consistent and accurate for predicting the 5-year OS of CC patients. Besides, METs were correlated with distant metastasis and inflammation. Through in vitro experiments, we confirmed that there was a positive feedback loop between CC cells and METs, in that METs promoted the invasion of CC cells and CC cells enhanced the production of METs, in turn. This interaction could be blocked by PAD2-IN-1 inhibitors. More importantly, animal experiments revealed that PAD2-IN-1 inhibited METs formation and CC liver metastasis in vivo.ConclusionsMETs were the potential biomarker of CC patient prognosis. PAD2-IN-1 inhibited the crosstalk between CC cells and METs in vitro and in vivo, which should be emphasized in CC therapy.Tianli ChenTianli ChenYue WangZhaodi NanJie WuAilu LiTingguo ZhangXun QuChen LiFrontiers Media S.A.articlecolon cancermacrophage extracellular traps (METs)prognosisPAD2PAD2-IN-1Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colon cancer macrophage extracellular traps (METs) prognosis PAD2 PAD2-IN-1 Immunologic diseases. Allergy RC581-607
spellingShingle	colon cancer macrophage extracellular traps (METs) prognosis PAD2 PAD2-IN-1 Immunologic diseases. Allergy RC581-607 Tianli Chen Tianli Chen Yue Wang Zhaodi Nan Jie Wu Ailu Li Tingguo Zhang Xun Qu Chen Li Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis
description	BackgroundMacrophage extracellular traps (METs) and tumor-infiltrating macrophages contribute to the progression of several diseases. But the role of METs and tumor-infiltrating macrophages in colon cancer (CC) has not been illuminated. In this study, we aimed to clarify the prognostic value of METs for CC patients and to explore the interaction between CC cells and METs in vitro and in vivo.MethodsA training cohort consisting of 116 patients and a validation cohort of 94 patients were enrolled in this study. Immunofluorescence (IF) staining was conducted to determine METs formation in CC patients. Cox regression was used to perform prognostic analysis and screen out the best prognostic model. A nomogram was established to predict 5-year overall survival (OS). The correlation between METs with clinicopathological features and inflammatory markers was analyzed. The formation of METs in vitro was detected by SYTOX® green and IF staining, and the effect of METs on CC cells was detected by transwell assays. PAD2-IN-1, a selective inhibitor of peptidylarginine deiminase 2 (PAD2), was introduced to destroy the crosstalk between CC cells and METs in vitro and in vivo.ResultsMETs levels were higher in CC tissues and were an independent prognostic factor for CC patients. The prognostic model consisting of age, tumors local invasion, lymph node metastasis and METs were confirmed to be consistent and accurate for predicting the 5-year OS of CC patients. Besides, METs were correlated with distant metastasis and inflammation. Through in vitro experiments, we confirmed that there was a positive feedback loop between CC cells and METs, in that METs promoted the invasion of CC cells and CC cells enhanced the production of METs, in turn. This interaction could be blocked by PAD2-IN-1 inhibitors. More importantly, animal experiments revealed that PAD2-IN-1 inhibited METs formation and CC liver metastasis in vivo.ConclusionsMETs were the potential biomarker of CC patient prognosis. PAD2-IN-1 inhibited the crosstalk between CC cells and METs in vitro and in vivo, which should be emphasized in CC therapy.
format	article
author	Tianli Chen Tianli Chen Yue Wang Zhaodi Nan Jie Wu Ailu Li Tingguo Zhang Xun Qu Chen Li
author_facet	Tianli Chen Tianli Chen Yue Wang Zhaodi Nan Jie Wu Ailu Li Tingguo Zhang Xun Qu Chen Li
author_sort	Tianli Chen
title	Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis
title_short	Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis
title_full	Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis
title_fullStr	Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis
title_full_unstemmed	Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis
title_sort	interaction between macrophage extracellular traps and colon cancer cells promotes colon cancer invasion and correlates with unfavorable prognosis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/19841d9db9994f3292dc8a4808be0318
work_keys_str_mv	AT tianlichen interactionbetweenmacrophageextracellulartrapsandcoloncancercellspromotescoloncancerinvasionandcorrelateswithunfavorableprognosis AT tianlichen interactionbetweenmacrophageextracellulartrapsandcoloncancercellspromotescoloncancerinvasionandcorrelateswithunfavorableprognosis AT yuewang interactionbetweenmacrophageextracellulartrapsandcoloncancercellspromotescoloncancerinvasionandcorrelateswithunfavorableprognosis AT zhaodinan interactionbetweenmacrophageextracellulartrapsandcoloncancercellspromotescoloncancerinvasionandcorrelateswithunfavorableprognosis AT jiewu interactionbetweenmacrophageextracellulartrapsandcoloncancercellspromotescoloncancerinvasionandcorrelateswithunfavorableprognosis AT ailuli interactionbetweenmacrophageextracellulartrapsandcoloncancercellspromotescoloncancerinvasionandcorrelateswithunfavorableprognosis AT tingguozhang interactionbetweenmacrophageextracellulartrapsandcoloncancercellspromotescoloncancerinvasionandcorrelateswithunfavorableprognosis AT xunqu interactionbetweenmacrophageextracellulartrapsandcoloncancercellspromotescoloncancerinvasionandcorrelateswithunfavorableprognosis AT chenli interactionbetweenmacrophageextracellulartrapsandcoloncancercellspromotescoloncancerinvasionandcorrelateswithunfavorableprognosis
_version_	1718404147916570624

Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis

Ejemplares similares