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A novel tdTomato transgenic mouse model to visualize FAP‐positive cancer‐associated fibroblasts

Authors :
Feng Wei
Tomoyuki Uchihara
Atsuko Yonemura
Noriko Yasuda‐Yoshihara
Tadahito Yasuda
Takashi Semba
Masahiro Fukuda
Takahiko Akiyama
Fumimasa Kitamura
Luke Bu
Xichen Hu
Lingfeng Fu
Jun Zhang
Ryusho Kariya
Juntaro Yamasaki
Kazuki Aihara
Kohei Yamashita
Osamu Nagano
Seiji Okada
Hideo Baba
Takatsugu Ishimoto
Source :
The FEBS Journal. 290:2604-2615
Publication Year :
2023
Publisher :
Wiley, 2023.

Abstract

Fibroblast activation protein (FAP) generally shows low or undetectable expression in most normal tissues but is highly expressed in fibroblasts in almost all carcinomas. FAP is one of the potential molecules to detect activated fibroblasts and has multiple roles in tumour progression. We generated transgenic mice that specifically expressed tdTomato along with FAP promoter activity. Coculturing a mouse gastric cancer cell line and FAP-tdTomato transgenic mouse-derived fibroblasts showed that tdTomato expression was elevated in the cocultured fibroblasts. Moreover, stomach wall transplanted tumours in mice also showed FAP-tdTomato expression in fibroblasts of the stomach and each metastatic legion. These results indicated that FAP-tdTomato expression in fibroblasts was elevated by stimulation through the interaction with cancer cells. Functionally, collagen production was increased in FAP/tdTomato-positive fibroblasts cocultured with mouse cancer cells. These FAP-tdTomato transgenic mice have the potential to be used to investigate real-time FAP dynamics and the importance of FAP expression in tumour development.

Details

ISSN :
17424658 and 1742464X
Volume :
290
Database :
OpenAIRE
Journal :
The FEBS Journal
Accession number :
edsair.doi.dedup.....c59a7d238441723e93e07808fbdfe61b