FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis
Language English Country Great Britain, England Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31699800
DOI
10.1242/dev.185306
PII: dev.185306
Knihovny.cz E-resources
- Keywords
- Branching morphogenesis, Collagen, Extracellular matrix, Fibroblast, Fibroblast growth factor, Mammary gland, Mouse, Stroma,
- MeSH
- Fibroblast Growth Factor 2 metabolism MeSH
- Fibroblast Growth Factor 9 metabolism MeSH
- Fibroblasts cytology metabolism MeSH
- MAP Kinase Signaling System * MeSH
- Mammary Glands, Animal cytology embryology MeSH
- Mice, Inbred ICR MeSH
- Mice MeSH
- Paracrine Communication * MeSH
- Receptor, Fibroblast Growth Factor, Type 1 metabolism MeSH
- Receptor, Fibroblast Growth Factor, Type 2 metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Fgf9 protein, mouse MeSH Browser
- Fgfr1 protein, mouse MeSH Browser
- Fgfr2 protein, mouse MeSH Browser
- Fibroblast Growth Factor 2 MeSH
- Fibroblast Growth Factor 9 MeSH
- Receptor, Fibroblast Growth Factor, Type 1 MeSH
- Receptor, Fibroblast Growth Factor, Type 2 MeSH
Fibroblast growth factor (FGF) signaling is crucial for mammary gland development. Although multiple roles for FGF signaling in the epithelium have been described, the function of FGF signaling in mammary stroma has not been elucidated. In this study, we investigated FGF signaling in mammary fibroblasts. We found that murine mammary fibroblasts express FGF receptors FGFR1 and FGFR2 and respond to FGF ligands. In particular, FGF2 and FGF9 induce sustained ERK1/2 signaling and promote fibroblast proliferation and migration in 2D cultures. Intriguingly, only FGF2 induces fibroblast migration in 3D extracellular matrix (ECM) through regulation of actomyosin cytoskeleton and promotes force-mediated collagen remodeling by mammary fibroblasts. Moreover, FGF2 regulates production of ECM proteins by mammary fibroblasts, including collagens, fibronectin, osteopontin and matrix metalloproteinases. Finally, using organotypic 3D co-cultures we show that FGF2 and FGF9 signaling in mammary fibroblasts enhances fibroblast-induced branching of mammary epithelium by modulating paracrine signaling, and that knockdown of Fgfr1 and Fgfr2 in mammary fibroblasts reduces branching of mammary epithelium. Our results demonstrate a pleiotropic role for FGF signaling in mammary fibroblasts, with implications for regulation of mammary stromal functions and epithelial branching morphogenesis.
References provided by Crossref.org
Fibroblast-Epithelium Co-culture Methods Using Epithelial Organoids and Cell Line-Derived Spheroids
Fibroblast-induced mammary epithelial branching depends on fibroblast contractility
An Organotypic Assay to Study Epithelial-Fibroblast Interactions in Human Breast
Single Organoids Droplet-Based Staining Method for High-End 3D Imaging of Mammary Organoids
Mammary Organoids and 3D Cell Cultures: Old Dogs with New Tricks
Primary Mammary Organoid Model of Lactation and Involution
