American Association for Cancer Research
00085472can183064-sup-209645_3_supp_5673308_pvkgxt.jpeg (465.03 kB)

Figure S3 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

Total FAK1 and STAT3 are present in KC;Prl-/- PanINs.



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.