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

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

doi:10.1111/febs.16712

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

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 BabaTakatsugu Ishimoto

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2604-2615
Number of pages	12
Journal	FEBS Journal
Volume	290
Issue number	10
DOIs	https://doi.org/10.1111/febs.16712
Publication status	Published - 05-2023
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/febs.16712

Cite this

Wei, F., Uchihara, T., Yonemura, A., Yasuda-Yoshihara, N., Yasuda, T., Semba, T., Fukuda, M., Akiyama, T., Kitamura, F., Bu, L., Hu, X., Fu, L., Zhang, J., Kariya, R., Yamasaki, J., Aihara, K., Yamashita, K., Nagano, O., Okada, S., ... Ishimoto, T. (2023). A novel tdTomato transgenic mouse model to visualize FAP-positive cancer-associated fibroblasts. FEBS Journal, 290(10), 2604-2615. https://doi.org/10.1111/febs.16712

@article{fcf6c1981f14457da00b67778aeec063,

title = "A novel tdTomato transgenic mouse model to visualize FAP-positive cancer-associated fibroblasts",

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.",

author = "Feng Wei and Tomoyuki Uchihara and Atsuko Yonemura and Noriko Yasuda-Yoshihara and Tadahito Yasuda and Takashi Semba and Masahiro Fukuda and Takahiko Akiyama and Fumimasa Kitamura and Luke Bu and Xichen Hu and Lingfeng Fu and Jun Zhang and Ryusho Kariya and Juntaro Yamasaki and Kazuki Aihara and Kohei Yamashita and Osamu Nagano and Seiji Okada and Hideo Baba and Takatsugu Ishimoto",

note = "Publisher Copyright: {\textcopyright} 2022 Federation of European Biochemical Societies.",

year = "2023",

month = may,

doi = "10.1111/febs.16712",

language = "English",

volume = "290",

pages = "2604--2615",

journal = "FEBS Journal",

issn = "1742-464X",

publisher = "John Wiley and Sons Inc.",

number = "10",

}

Wei, F, Uchihara, T, Yonemura, A, Yasuda-Yoshihara, N, Yasuda, T, Semba, T, Fukuda, M, Akiyama, T, Kitamura, F, Bu, L, Hu, X, Fu, L, Zhang, J, Kariya, R, Yamasaki, J, Aihara, K, Yamashita, K, Nagano, O, Okada, S, Baba, H & Ishimoto, T 2023, 'A novel tdTomato transgenic mouse model to visualize FAP-positive cancer-associated fibroblasts', FEBS Journal, vol. 290, no. 10, pp. 2604-2615. https://doi.org/10.1111/febs.16712

TY - JOUR

T1 - A novel tdTomato transgenic mouse model to visualize FAP-positive cancer-associated fibroblasts

AU - Wei, Feng

AU - Uchihara, Tomoyuki

AU - Yonemura, Atsuko

AU - Yasuda-Yoshihara, Noriko

AU - Yasuda, Tadahito

AU - Semba, Takashi

AU - Fukuda, Masahiro

AU - Akiyama, Takahiko

AU - Kitamura, Fumimasa

AU - Bu, Luke

AU - Hu, Xichen

AU - Fu, Lingfeng

AU - Zhang, Jun

AU - Kariya, Ryusho

AU - Yamasaki, Juntaro

AU - Aihara, Kazuki

AU - Yamashita, Kohei

AU - Nagano, Osamu

AU - Okada, Seiji

AU - Baba, Hideo

AU - Ishimoto, Takatsugu

PY - 2023/5

Y1 - 2023/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85145483978&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85145483978&partnerID=8YFLogxK

U2 - 10.1111/febs.16712

DO - 10.1111/febs.16712

M3 - Article

C2 - 36565059

AN - SCOPUS:85145483978

SN - 1742-464X

VL - 290

SP - 2604

EP - 2615

JO - FEBS Journal

JF - FEBS Journal

IS - 10

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this