IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma

Abstract The precise role of tumor associated macrophages remains unclear in pancreatic ductal adenocarcinoma (PDAC) while TGF-ß has an unclear role in metastases formation. In order to understand the role of IL23, an interleukin associated with macrophage polarization, we investigated IL23 in the c...

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Autores principales:	S. Mazher Hussain, Leighton F. Reed, Bradley A. Krasnick, Gustavo Miranda-Carboni, Ryan C. Fields, Ye Bi, Abul Elahi, Abidemi Ajidahun, Paxton V. Dickson, Jeremiah L. Deneve, William G. Hawkins, David Shibata, Evan S. Glazer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2c45e38378414554acde032d45cd7d03
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spelling	oai:doaj.org-article:2c45e38378414554acde032d45cd7d032021-12-02T15:08:14ZIL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma10.1038/s41598-018-24194-52045-2322https://doaj.org/article/2c45e38378414554acde032d45cd7d032018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24194-5https://doaj.org/toc/2045-2322Abstract The precise role of tumor associated macrophages remains unclear in pancreatic ductal adenocarcinoma (PDAC) while TGF-ß has an unclear role in metastases formation. In order to understand the role of IL23, an interleukin associated with macrophage polarization, we investigated IL23 in the context of TGF-ß expression in PDAC. We hypothesized that IL23 expression is associated with metastatic development and survival in PDAC. We investigated IL23 and TGF-ß protein expression on resected PDAC patient tumor sections who were divided into short-term (<12 months) survivors and long-term (>30 months) survivors. Panc-1 cells treated with IL23, TGF-ß, macrophages, or combinations thereof, were orthotopically implanted into NSG mice. Patients in the long-term survivor group had higher IL23 protein expression (P = 0.01). IL23 expression was linearly correlated with TGF-ß expression in patients in the short-term survivor group (P = 0.038). Macrophages induce a higher rate of PDAC metastasis in the mouse model (P = 0.02), which is abrogated by IL23 and TGF-ß treatment (P < 0.001). Macrophages serve a critical role in PDAC tumor growth and metastasis. TGF-ß contributes to a less tumorigenic TME through regulation of macrophages. Macrophages increases PDAC primary tumor growth and metastases formation while combined IL23 and TGF-ß pre-treatment diminishes these processes.S. Mazher HussainLeighton F. ReedBradley A. KrasnickGustavo Miranda-CarboniRyan C. FieldsYe BiAbul ElahiAbidemi AjidahunPaxton V. DicksonJeremiah L. DeneveWilliam G. HawkinsDavid ShibataEvan S. GlazerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q S. Mazher Hussain Leighton F. Reed Bradley A. Krasnick Gustavo Miranda-Carboni Ryan C. Fields Ye Bi Abul Elahi Abidemi Ajidahun Paxton V. Dickson Jeremiah L. Deneve William G. Hawkins David Shibata Evan S. Glazer IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma
description	Abstract The precise role of tumor associated macrophages remains unclear in pancreatic ductal adenocarcinoma (PDAC) while TGF-ß has an unclear role in metastases formation. In order to understand the role of IL23, an interleukin associated with macrophage polarization, we investigated IL23 in the context of TGF-ß expression in PDAC. We hypothesized that IL23 expression is associated with metastatic development and survival in PDAC. We investigated IL23 and TGF-ß protein expression on resected PDAC patient tumor sections who were divided into short-term (<12 months) survivors and long-term (>30 months) survivors. Panc-1 cells treated with IL23, TGF-ß, macrophages, or combinations thereof, were orthotopically implanted into NSG mice. Patients in the long-term survivor group had higher IL23 protein expression (P = 0.01). IL23 expression was linearly correlated with TGF-ß expression in patients in the short-term survivor group (P = 0.038). Macrophages induce a higher rate of PDAC metastasis in the mouse model (P = 0.02), which is abrogated by IL23 and TGF-ß treatment (P < 0.001). Macrophages serve a critical role in PDAC tumor growth and metastasis. TGF-ß contributes to a less tumorigenic TME through regulation of macrophages. Macrophages increases PDAC primary tumor growth and metastases formation while combined IL23 and TGF-ß pre-treatment diminishes these processes.
format	article
author	S. Mazher Hussain Leighton F. Reed Bradley A. Krasnick Gustavo Miranda-Carboni Ryan C. Fields Ye Bi Abul Elahi Abidemi Ajidahun Paxton V. Dickson Jeremiah L. Deneve William G. Hawkins David Shibata Evan S. Glazer
author_facet	S. Mazher Hussain Leighton F. Reed Bradley A. Krasnick Gustavo Miranda-Carboni Ryan C. Fields Ye Bi Abul Elahi Abidemi Ajidahun Paxton V. Dickson Jeremiah L. Deneve William G. Hawkins David Shibata Evan S. Glazer
author_sort	S. Mazher Hussain
title	IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma
title_short	IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma
title_full	IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma
title_fullStr	IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma
title_full_unstemmed	IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma
title_sort	il23 and tgf-ß diminish macrophage associated metastasis in pancreatic carcinoma
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/2c45e38378414554acde032d45cd7d03
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IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma

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