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

J 2019

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

SUMBAL, Jakub a Zuzana KOLEDOVÁ

Základní údaje

Originální název

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

Autoři

SUMBAL, Jakub (203 Česká republika, domácí) a Zuzana KOLEDOVÁ (703 Slovensko, garant, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10605 Developmental biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.611

Kód RIV

RIV/00216224:14110/19:00108153

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1242/dev.185306

UT WoS

000507575700017

Klíčová slova anglicky

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

Štítky

14110517, CF CELLIM, rivok

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

Anotace

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.

Návaznosti

GJ16-20031Y, projekt VaV

Název: Signalizace FGF ve fibroblastech mléčné žlázy a její úloha ve vývoji a nádorech mléčné žlázy

Investor: Grantová agentura ČR, Signalizace FGF ve fibroblastech mléčné žlázy a její úloha ve vývoji a nádorech mléčné žlázy

MUNI/E/0519/2019, interní kód MU

Název: The role of fibroblasts and FGF signaling in mammary gland development: Upgrade and finalization of publication

Investor: Masarykova univerzita, The role of fibroblasts and FGF signaling in mammary gland development: Upgrade and finalization of publication, Podpora zvýšení kvality vynikajících výsledků

ROZV/24/LF/2018, interní kód MU

Název: LF - Příspěvek na IP 2108

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, LF - Příspěvek na IP 2108, Interní rozvojové projekty

Citovat

SUMBAL, Jakub a Zuzana KOLEDOVÁ. FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis. Development. CAMBRIDGE: COMPANY BIOLOGISTS LTD, 2019, roč. 143, č. 23, s. 1-16. ISSN 0950-1991. Dostupné z: https://dx.doi.org/10.1242/dev.185306.

@article{1623296,
   author = {Sumbal, Jakub and Koledová, Zuzana},
   article_location = {CAMBRIDGE},
   article_number = {23},
   doi = {http://dx.doi.org/10.1242/dev.185306},
   keywords = {Branching morphogenesis; Collagen; Extraceliular matrix; Fibroblast; Fibroblast growth factor; Mammary gland; Stroma; Mouse},
   language = {eng},
   issn = {0950-1991},
   journal = {Development},
   title = {FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis},
   url = {http://dx.doi.org/10.1242/dev.185306},
   volume = {143},
   year = {2019}
}

TY  - JOUR
ID  - 1623296
AU  - Sumbal, Jakub - Koledová, Zuzana
PY  - 2019
TI  - FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis
JF  - Development
VL  - 143
IS  - 23
SP  - 1-16
EP  - 1-16
PB  - COMPANY BIOLOGISTS LTD
SN  - 09501991
KW  - Branching morphogenesis
KW  - Collagen
KW  - Extraceliular matrix
KW  - Fibroblast
KW  - Fibroblast growth factor
KW  - Mammary gland
KW  - Stroma
KW  - Mouse
UR  - http://dx.doi.org/10.1242/dev.185306
L2  - http://dx.doi.org/10.1242/dev.185306
N2  - 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.
ER  -

SUMBAL, Jakub a Zuzana KOLEDOVÁ. FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis. \textit{Development}. CAMBRIDGE: COMPANY BIOLOGISTS LTD, 2019, roč.~143, č.~23, s.~1-16. ISSN~0950-1991. Dostupné z: https://dx.doi.org/10.1242/dev.185306.

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