American Association for Cancer Research
00085472can183064-sup-209645_3_supp_5673500_pvkgxt.jpeg (114.03 kB)

Figure S1 from Prolactin Promotes Fibrosis and Pancreatic Cancer Progression

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posted on 2023-03-31, 02:46 authored by Manuj Tandon, Gina M. Coudriet, Angela Criscimanna, Mairobys Socorro, Mouhanned Eliliwi, Aatur D. Singhi, Zobeida Cruz-Monserrate, Peter Bailey, Michael T. Lotze, Herbert Zeh, Jing Hu, Vincent Goffin, George K. Gittes, Andrew V. Biankin, Farzad Esni

Prolactin does not promote activation of Jak2 signaling pathway in BxPC3 cell line, which lacks PRLR expression.



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. Prolactin is a key factor in the cross-talk between the stroma and neoplastic epithelium, functioning to promote fibrosis and PDAC progression.