Prolactin Promotes Fibrosis and Pancreatic Cancer Progression

Cancer Research
Manuj TandonFarzad Esni

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.

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Citations

Sep 5, 2020·Immunity, Inflammation and Disease·Andrea F CruzFarzad Esni
Mar 5, 2021·Reviews in the Neurosciences·Edgar Ramos-MartinezMarco Cerbon
Oct 29, 2020·Seminars in Cell & Developmental Biology·Ödül Karayazi AtıcıCarrie S Shemanko

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