Cancer research (Chicago, Ill.), 2019-10, Vol.79 (20), p.5316-5327
2019
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- Autor(en) / Beteiligte
- Titel
- Prolactin Promotes Fibrosis and Pancreatic Cancer Progression
- Ist Teil von
- Cancer research (Chicago, Ill.), 2019-10, Vol.79 (20), p.5316-5327
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2019
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445DOI: 10.1158/0008-5472.CAN-18-3064Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6801092
- Format
- –
- Schlagworte
- Animals, Carcinoma, Pancreatic Ductal - pathology, Carcinoma, Pancreatic Ductal - physiopathology, Cell Line, Tumor, Collagen - metabolism, Disease Progression, Epithelium - metabolism, Female, Fibrosis, Focal Adhesion Kinase 1 - metabolism, Genes, Reporter, HMGB1 Protein - physiology, Humans, Macrophages - metabolism, Male, Metoclopramide, Mice, Mice, Knockout, Neoplasm Proteins - metabolism, Neoplasms, Hormone-Dependent - pathology, Neoplasms, Hormone-Dependent - physiopathology, Pancreatic Neoplasms - pathology, Pancreatic Neoplasms - physiopathology, Phosphorylation, Pregnancy, Prolactin - deficiency, Prolactin - pharmacology, Prolactin - physiology, Protein Processing, Post-Translational, Receptors, Prolactin - genetics, Receptors, Prolactin - metabolism, Recombinant Proteins - pharmacology, RNA Interference, RNA, Small Interfering - genetics, STAT3 Transcription Factor - metabolism, Stromal Cells - metabolism