| Autor: |
Farzad Esni, Andrew V. Biankin, George K. Gittes, Vincent Goffin, Jing Hu, Herbert Zeh, Michael T. Lotze, Peter Bailey, Zobeida Cruz-Monserrate, Aatur D. Singhi, Mouhanned Eliliwi, Mairobys Socorro, Angela Criscimanna, Gina M. Coudriet, Manuj Tandon |
| Rok vydání: |
2023 |
| DOI: |
10.1158/0008-5472.c.6511281.v1 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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