A novel tdTomato transgenic mouse model to visualize FAP‐positive cancer‐associated fibroblasts
A novel tdTomato transgenic mouse model to visualize FAP‐positive cancer‐associated fibroblasts
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DOI：
10.1111/febs.16712
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发表时间：
2022-12
期刊：
影响因子：
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通讯作者：
Feng Wei;Tomoyuki Uchihara;Atsuko Yonemura;Noriko Yasuda-Yoshihara;Tadahito Yasuda;T. Semba;Masahiro Fukuda;T. Akiyama;Fumimasa Kitamura;L. Bu;Xichen Hu;Lingfeng Fu;Jun Zhang;R. Kariya;Juntaro Yamasaki;Kazuki Aihara;Kohei Yamashita;O. Nagano;S. Okada;Hideo Baba;T. Ishimoto
中科院分区：
文献类型：
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作者：
Feng Wei;Tomoyuki Uchihara;Atsuko Yonemura;Noriko Yasuda-Yoshihara;Tadahito Yasuda;T. Semba;Masahiro Fukuda;T. Akiyama;Fumimasa Kitamura;L. Bu;Xichen Hu;Lingfeng Fu;Jun Zhang;R. Kariya;Juntaro Yamasaki;Kazuki Aihara;Kohei Yamashita;O. Nagano;S. Okada;Hideo Baba;T. Ishimoto
成纤维细胞活化蛋白（FAP）在大多数正常组织中通常表现为低表达或无法检测到，但在几乎所有癌症的成纤维细胞中都有高表达。FAP是检测活化成纤维细胞的潜在分子之一，在肿瘤进展中具有多种作用。我们产生了特异性表达tdTomato和FAP启动子活性的转基因小鼠。将小鼠胃癌细胞系与FAP - tdTomato转基因小鼠来源的成纤维细胞共培养发现，共培养的成纤维细胞中tdTomato的表达升高。此外，小鼠胃壁移植肿瘤在胃成纤维细胞和每个转移军团中也显示FAP - tdTomato表达。这些结果表明FAP - tdTomato在成纤维细胞中的表达通过与癌细胞相互作用的刺激而升高。功能上，FAP/tdTomato阳性成纤维细胞与小鼠癌细胞共培养，胶原生成增加。这些FAP - tdTomato转基因小鼠有潜力用于研究实时FAP动态和FAP表达在肿瘤发展中的重要性。
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.