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Creating a Real-World Tumor Microenvironment Model
Cancer is a complex tissue composed of cancer cells and their surrounding non-cancerous cells. Therefore, to reproduce the human tumor microenvironment, it is necessary to establish an assay system that includes not only cancer cells but also non-cancer cells.
In this field, we are focusing on fibroblasts (CAFs), which are representative of non-cancer cells. Recent studies have shown that CAFs are a functionally and morphologically heterogeneous population of cells. We have isolated and cultured CAFs from many cancer specimens and constructed a real-world model of the microenvironment formed by these CAFs and cancer cells using fluorescent proteins, time lapse imaging, and organoid production techniques to elucidate the mechanism of cancer development and drug sensitivity.
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- Yoshida T, Ishii G, Goto K, Neri S, Hashimoto H, Yoh K, Niho S, Umemura S, Matsumoto S, Ohmatsu H, Iida S, Niimi A, Nagai K, Ohe Y, Ochiai A. Podoplanin-positive cancer-associated fibroblasts in the tumor microenvironment induce primary resistance to EGFR-TKIs in lung adenocarcinoma with EGFR mutation. Clin. Cancer Res, 21(3):642-51, 2015
- Hoshino A, Ishii G, Ito T, Aoyagi K, Ohtaki Y, Nagai K, Sasaki H, Ochiai A. Podoplanin-positive fibroblasts enhance lung adenocarcinoma tumor formation. Cancer Res, 71:4769-79, 2011
- Neri S, Miyashita T, Hashimoto H, Suda Y, Ishibashi M, Kii H, Watanabe H, Kuwata T, Tsuboi M, Goto K, Menju T, Sonobe M, Date H, Ochiai A, Ishii G. Fibroblast-led cancer cell invasion is activated by epithelial-mesenchymal transition through platelet-derived growth factor BB secretion of lung adenocarcinoma. Cancer Lett, 395:20-30, 2017
- Nakamura H, Sugano M, Miyashita T, Hashimoto H, Ochiai A, Suzuki K, Tsuboi M, Ishii G. Organoid culture containing cancer cells and stromal cells reveals that podoplanin-positive cancer-associated fibroblasts enhance proliferation of lung cancer cells. Lung Cancer, 134:100-107, 2019
- Miyashita T, Neri S, Hashimoto H, Akutsu A, Sugano M, Fujii S, Ochiai A, Ishii G. Fibroblasts-dependent invasion of podoplanin-positive cancer stem cells in squamous cell carcinoma. J Cell Physiol, 2020 Online ahead of print.