| Literature DB >> 31395607 |
Manuj Tandon1,2, Gina M Coudriet1,2, Angela Criscimanna1,2, Mairobys Socorro1,2, Mouhanned Eliliwi1,2, Aatur D Singhi3, Zobeida Cruz-Monserrate4, Peter Bailey5, Michael T Lotze1,6, Herbert Zeh1,6, Jing Hu6,7, Vincent Goffin8, George K Gittes1,2, Andrew V Biankin5,9,10, Farzad Esni11,2,6.
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. SIGNIFICANCE: Prolactin is a key factor in the cross-talk between the stroma and neoplastic epithelium, functioning to promote fibrosis and PDAC progression. ©2019 American Association for Cancer Research.Entities:
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Year: 2019 PMID： 31395607 PMCID： PMC6801092 DOI： 10.1158/0008-5472.CAN-18-3064
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701