Cited by 405Pancreatic and Hepatic Oncology ResearchPancreatitis Pathology and TreatmentCytokine Signaling Pathways and Interactions

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Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia

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McAllister, Florencia, Bailey, Jennifer M., Alsina, Janivette, Nirschl, Christopher J., Sharma, Rajni, Fan, Hongni, Rattigan, Yanique, Roeser, Jeffrey C., Lankapalli, Rachana H., Zhang, Hao, Jaffee, Elizabeth M., Drake, Charles G., Housseau, Franck, Maitra, Anirban, Kolls, Jay K., Sears, Cynthia L., Pardoll, Drew M., Leach, Steven D.·2014·Cancer Cell

DOI 10.1016/j.ccr.2014.03.014PMC PMC4072043

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Abstract

Many human cancers are dramatically accelerated by chronic inflammation. However, the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that Kras(G12D) induces expression of functional IL-17 receptors on PanIN epithelial cells and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation.

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Authors: McAllister, F., Bailey, J. M., Alsina, J., Nirschl, C. J., Sharma, R., Fan, H., Rattigan, Y., Roeser, J. C., Lankapalli, R. H., Zhang, H., Jaffee, E. M., Drake, C. G., Housseau, F., Maitra, A., Kolls, J. K., Sears, C. L., Pardoll, D. M., & Leach, S. D.
Affiliations: Johns Hopkins University (US)
Children's Hospital of Pittsburgh (US)
Corresponding author: Leach, Steven D.
ORCID: McAllister, Florencia
Bailey, Jennifer M.
Nirschl, Christopher J.
Sharma, Rajni
Fan, Hongni
Zhang, Hao
Jaffee, Elizabeth M.
Drake, Charles G.
Housseau, Franck
Maitra, Anirban
Kolls, Jay K.
Sears, Cynthia L.
Leach, Steven D.
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2014-05
Volume: 25
Issue: 5
Pages: 621-637
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2014.03.014
PMC: PMC4072043
OpenAlex: W2085605492
Cited by: 405
References: 63
Citations by year: 2026: 21 · 2025: 27 · 2024: 39 · 2023: 37 · 2022: 43 · 2021: 38 · 2020: 44 · 2019: 37 · 2018: 15 · 2017: 32 · 2016: 29 · 2015: 29 · 2014: 14
FWCI: 16.71
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 376 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Amgen
National Cancer Institute (P01CA134292, T32CA126607, F32CA157044)
National Institute of General Medical Sciences (T32GM066691)
National Institute of Allergy and Infectious Diseases (T32AI007247)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK097087)
National Center for Research Resources (S10RR017933)
Topics: Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: KRAS G12D, IL-17 signaling, pancreatic intraepithelial neoplasia, chronic pancreatitis, IL-17 receptor, pancreatic stroma, chronic inflammation, IL-17 inhibition
MeSH terms: Animals, Carcinoma in Situ, Cell Transformation, Neoplastic, Epithelial Cells, Hematopoietic System, Humans, Inflammation, Mice, Transgenic, Pancreas, Pancreatic Neoplasms, Signal Transduction, Proto-Oncogene Proteins p21(ras), Receptors, Antigen, T-Cell, gamma-delta, Chemoprevention, Interleukin-17, Mice, Receptors, Interleukin-17, Th17 Cells

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Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia

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