J 2019

FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis

SUMBAL, Jakub and Zuzana KOLEDOVÁ

Basic information

Original name

FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis

Authors

SUMBAL, Jakub (203 Czech Republic, belonging to the institution) and Zuzana KOLEDOVÁ (703 Slovakia, guarantor, belonging to the institution)

Edition

Development, CAMBRIDGE, COMPANY BIOLOGISTS LTD, 2019, 0950-1991

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10605 Developmental biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.611

RIV identification code

RIV/00216224:14110/19:00108153

Organization unit

Faculty of Medicine

DOI

UT WoS

000507575700017

Keywords in English

Branching morphogenesis; Collagen; Extraceliular matrix; Fibroblast; Fibroblast growth factor; Mammary gland; Stroma; Mouse

Tags

Změněno: 17/2/2020 15:01, Mgr. Tereza Miškechová

Abstract

V originále

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.

Links

GJ16-20031Y, research and development project
Name: Signalizace FGF ve fibroblastech mléčné žlázy a její úloha ve vývoji a nádorech mléčné žlázy
Investor: Czech Science Foundation
MUNI/E/0519/2019, interní kód MU
Name: The role of fibroblasts and FGF signaling in mammary gland development: Upgrade and finalization of publication
Investor: Masaryk University, Promoting quality excellence
ROZV/24/LF/2018, interní kód MU
Name: LF - Příspěvek na IP 2108
Investor: Ministry of Education, Youth and Sports of the CR, Internal development projects