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

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 Deneve, William G. Hawkins, David Shibata, Evan Glazer

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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.

Original languageEnglish (US)
Article number5808
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Adenocarcinoma
Macrophages
Neoplasm Metastasis
Survivors
Neoplasms
Interleukins
Growth
Pancreatic Carcinoma
Proteins
Survival
Therapeutics

All Science Journal Classification (ASJC) codes

  • General

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IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma. / Hussain, S. Mazher; Reed, Leighton F.; Krasnick, Bradley A.; Miranda-Carboni, Gustavo; Fields, Ryan C.; Bi, Ye; Elahi, Abul; Ajidahun, Abidemi; Dickson, Paxton V.; Deneve, Jeremiah; Hawkins, William G.; Shibata, David; Glazer, Evan.

In: Scientific reports, Vol. 8, No. 1, 5808, 01.12.2018.

Research output: Contribution to journalArticle

Hussain, SM, Reed, LF, Krasnick, BA, Miranda-Carboni, G, Fields, RC, Bi, Y, Elahi, A, Ajidahun, A, Dickson, PV, Deneve, J, Hawkins, WG, Shibata, D & Glazer, E 2018, 'IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma', Scientific reports, vol. 8, no. 1, 5808. https://doi.org/10.1038/s41598-018-24194-5
Hussain, S. Mazher ; Reed, Leighton F. ; Krasnick, Bradley A. ; Miranda-Carboni, Gustavo ; Fields, Ryan C. ; Bi, Ye ; Elahi, Abul ; Ajidahun, Abidemi ; Dickson, Paxton V. ; Deneve, Jeremiah ; Hawkins, William G. ; Shibata, David ; Glazer, Evan. / IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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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.",
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