FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F19%3A00108153" target="_blank" >RIV/00216224:14110/19:00108153 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1242/dev.185306" target="_blank" >http://dx.doi.org/10.1242/dev.185306</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1242/dev.185306" target="_blank" >10.1242/dev.185306</a>
Alternative languages
Result language
angličtina
Original language name
FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10605 - Developmental biology
Result continuities
Project
<a href="/en/project/GJ16-20031Y" target="_blank" >GJ16-20031Y: FGF signalling in mammary fibroblasts and its role in mammary gland development and cancer</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Development
ISSN
0950-1991
e-ISSN
1477-9129
Volume of the periodical
143
Issue of the periodical within the volume
23
Country of publishing house
GB - UNITED KINGDOM
Number of pages
16
Pages from-to
1-16
UT code for WoS article
000507575700017
EID of the result in the Scopus database
2-s2.0-85077395213