@article{aac60c28022a4a13b008c97c7bc3ebb4,
title = "Prolactin promotes fibrosis and pancreatic cancer progression",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is associated with significant fibrosis. Recent findings have highlighted the profibrotic activity of tissue-resident macrophages in the pancreatic cancer microenvironment. Here, we show that neoplastic pancreatic epithelium, as well as a subset of tissue-resident macrophages, expresses the prolactin-receptor (PRLR). High mobility group box 1-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 IL6, a known major activator of STAT3, could represent a novel therapeutic strategy for treating pancreatic cancer.",
author = "Manuj Tandon and Coudriet, {Gina M.} and Angela Criscimanna and Mairobys Socorro and Mouhanned Eliliwi and Singhi, {Aatur D.} and Zobeida Cruz-Monserrate and Peter Bailey and Lotze, {Michael T.} and Herbert Zeh and Jing Hu and Vincent Goffin and Gittes, {George K.} and Biankin, {Andrew V.} and Farzad Esni",
note = "Funding Information: This study was supported by NIH/NIDDK grant DK101413 (to F. Esni); National Pancreas Foundation (to F. Esni); The Children's Hospital of Pittsburgh of UPMC (to F. Esni); Cancer Research UK C29717/A17263, C29717/A18484, C596/A18076, C596/A20921, and A23526 (to A.V. Biankin); Wellcome Trust Senior Investigator Award 103721/Z/14/Z (to A.V. Biankin); Pancreatic Cancer UK Future Research Leaders Fund FLF2015_04_Glasgow (to A.V. Biankin); Scottish Genome Partnership SEHHD-CSO 1175759/2158447 (to A.V. Biankin); MRC/EPSRC Glasgow Molecular Pathology Node (to Funding Information: This study was supported by NIH/NIDDK grant DK101413 (to F. Esni); National Pancreas Foundation (to F. Esni); The Children's Hospital of Pittsburgh of UPMC (to F. Esni); Cancer Research UK C29717/A17263, C29717/A18484, C596/A18076, C596/A20921, and A23526 (to A.V. Biankin); Wellcome Trust Senior Investigator Award 103721/Z/14/Z (to A.V. Biankin); Pancreatic Cancer UK Future Research Leaders Fund FLF2015_04_Glasgow (to A.V. Biankin); Scottish Genome Partnership SEHHD-CSO 1175759/2158447 (to A.V. Biankin); MRC/EPSRC Glasgow Molecular Pathology Node (to A.V. Biankin); and The Howat Foundation (to A.V. Biankin). We acknowledge the Comparative Pathology and Mouse Phenotyping Shared Resource (CPMPSR) of The Ohio State University Comprehensive Cancer Center for excellent immunohistochemical (Alan Flechtner and Florinda Jaynes) support. The work was supported in part by Cancer Center Support Grant P30 CA016058, National Cancer Institute, Bethesda, Maryland. We would like to thank Joshua Michel for helping us with the flow cytometry analyses. Publisher Copyright: {\textcopyright} 2019 American Association for Cancer Research.",
year = "2019",
month = oct,
day = "15",
doi = "10.1158/0008-5472.CAN-18-3064",
language = "English (US)",
volume = "79",
pages = "5316--5327",
journal = "Cancer Research",
issn = "0008-5472",
number = "20",
}