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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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
Article number5808
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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