The BAFF/NFκB axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts

• Material Type: 博士論文
• Title: The BAFF/NFκB axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts
• Author/Editor: Gao, Luping; Morine, Yuji; Yamada, Shinichiro; Saito, Yu; Ikemoto, Tetsuya; Tokuda, Kazunori; Miyazaki, Katsuki; Okikawa, Shouhei; Takasu, Chie; Shimada, Mitsuo
• Author Heading: Gao, Luping; Morine, Yuji; Yamada, Shinichiro; Saito, Yu; Ikemoto, Tetsuya; Tokuda, Kazunori; Miyazaki, Katsuki; Okikawa, Shouhei; Takasu, Chie; Shimada, Mitsuo
• Publication, Distribution, etc.: Wiley|Japanese Cancer Association
• Publication Date: 2021-06-22
• Publication Date (W3CDTF): 2021-06-22
• Alternative Title: BAFF/NFκB経路はソラフェニブ耐性肝癌と癌関連線維芽細胞の相互作用に重要である
• Periodical title: Cancer Science
• No. or year of volume/issue: 112 9
• Volume: 112
• Issue: 9
• Pages: 3545-3554
• ISSN (Periodical Title): ISSN : 1349-7006
• Degree grantor/type: 徳島大学
• Date Granted: 2021-09-30
• Dissertation Number: 甲第3558号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: B-cell activating factor; cancer-associated fibroblasts; hepatocellular carcinoma; drug resistance; sorafenib
• Target Audience: 一般
• Note (General): The tumor microenvironment affects malignancy in hepatocellular carcinoma (HCC) cells, and cancer-associated fibroblasts (CAFs) play an important role in the microenvironment. As recent studies indicated a difference between CAFs isolated from chemoresistant and non-resistant cancer tissues, therefore we investigated the intracellular mechanism in resistant HCC co-cultured CAFs and interactions between these CAFs with cancer cells. We established a sorafenib-resistant (SR) Huh7 (human HCC) cell line, and characterized it with cytokine assays, then developed CAFs by co-culturing human hepatic stellate cells with resistant or parental Huh7 cells. The 2 types of CAFs were co-cultured with parental Huh7 cells, thereafter the cell viability of these Huh7 cells was checked under sorafenib treatment. The SR Huh7 (Huh7SR) cells expressed increased B-cell activating factor (BAFF), which promoted high expression of CAF-specific markers in Huh7SR-co-cultured CAFs, showed activated BAFF, BAFF-R, and downstream of the NFκB-Nrf2 pathway, and aggravated invasion, migration, and drug resistance in co-cultured Huh7 cells. When we knocked down BAFF expression in Huh7SR cells, the previously increased malignancy and BAFF/NFκB axis in Huh7SR-co-cultured CAFs reversed, and enhanced chemoresistance in co-cultured Huh7 cells returned as well. In conclusion, the BAFF/NFκB pathway was activated in CAFs co-cultured with cell-culture medium from resistant Huh7, which promoted chemoresistance, and increased the malignancy in co-cultured non-resistant Huh7 cells. This suggests that the BAFF/NFκB axis in CAFs might be a potential therapeutic target in chemoresistance of HCC.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
• Related Material (DOI): 10.1111/cas.15041
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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