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

Autor: Wei F; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Uchihara T; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Yonemura A; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Yasuda-Yoshihara N; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Yasuda T; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Semba T; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Fukuda M; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan.; Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore City, Singapore., Akiyama T; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Kitamura F; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Bu L; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Hu X; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Fu L; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Zhang J; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan., Kariya R; Division of Haematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Japan., Yamasaki J; Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan., Aihara K; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan.; Department of Surgery, National Defense Medical College, Saitama, Japan., Yamashita K; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan., Nagano O; Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan., Okada S; Division of Haematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Japan., Baba H; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Japan., Ishimoto T; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Japan.
Jazyk: angličtina
Zdroj: The FEBS journal [FEBS J] 2023 May; Vol. 290 (10), pp. 2604-2615. Date of Electronic Publication: 2023 Jan 03.
DOI: 10.1111/febs.16712
Abstrakt: 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.
(© 2022 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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