Prolactin promotes fibrosis and pancreatic cancer progression

Tandon, M. et al. (2019) Prolactin promotes fibrosis and pancreatic cancer progression. Cancer Research, 79(20), pp. 5316-5327. (doi:10.1158/0008-5472.CAN-18-3064) (PMID:31395607)

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is associated with significant fibrosis. Recent findings have highlighted the pro-fibrotic activity of tissue-resident macrophages in the pancreatic cancer microenvironment. Here, we showed that neoplastic pancreatic epithelium, as well as a subset of tissue-resident macrophages, express the prolactin receptor (PRLR). HMGB1-induced prolactin expression in the pancreas maintained FAK1 and STAT3 phosphorylation within the epithelium and stroma. Gain-of-function and loss-of-function experiments demonstrated the essential role of prolactin in promoting collagen deposition, and fibrosis. Finally, the signaling cascade downstream of Prolactin/PRLR activated STAT3 rather than STAT5 in PDAC. These findings suggest that targeting prolactin together with IL-6, a known major activator of STAT3, could represent a novel therapeutic strategy for treating pancreatic cancer.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Biankin, Professor Andrew and Bailey, Dr Peter
Authors: Tandon, M., Coudriet, G. M., Criscimanna, A., Socorro, M., Eliliwi, M., Singhi, A. D., Cruz-Monserrate, Z., Bailey, P., Lotze, M. T., Zeh, H., Hu, J., Goffin, V., Gittes, G. K., Biankin, A. V., and Esni, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cancer Research
Publisher:American Association for Cancer Research
ISSN:0008-5472
ISSN (Online):1538-7445
Published Online:08 August 2019

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
169396Genotype Guided Stratified Therapy for Pancreatic CancerAndrew BiankinCancer Research UK (CRUK)C29717/A17263Institute of Cancer Sciences
169638Genotype Guided Stratified Therapy for Pancreatic CancerAndrew BiankinCancer Research UK (CRUK)C29717/A18484CS -Translational Research Centre
190874CR-UK Centre renewalKaren VousdenNot Applicable (NA)C596/A18076Institute of Cancer Sciences
172008Clinical Training Award Cycle 2Andrew BiankinCancer Research UK (CRUK)C596/A20921CS -Translational Research Centre
174160Precision PancAndrew BiankinCancer Research UK (CRUK)C29717/A23526CS -Translational Research Centre
170634Defining Platinum and PARP Responsive Molecular Phenotypes of Pancreatic Cancer.Andrew BiankinWellcome Trust (WELLCOTR)103721/Z/14/ZInstitute of Cancer Sciences