Oxidized high mobility group B-1 enhances metastability of colorectal cancer via modification of mesenchymal stem/ stromal cells

• Material Type: 博士論文
• Title: Oxidized high mobility group B-1 enhances metastability of colorectal cancer via modification of mesenchymal stem/ stromal cells
• Author/Editor: Kishi, Shingo; Fujiwara-Tani, Rina; Honoki, Kanya; Sasaki, Rika; Mori, Shiori; Ohmori, Hitoshi; Sasaki, Takamitsu; Miyagawa, Yoshihiro; Kawahara, Isao; Kido, Akira; Tanaka, Yasuhito; Kuniyasu, Hiroki
• Author Heading: Kishi, Shingo; Fujiwara-Tani, Rina; Honoki, Kanya; Sasaki, Rika; Mori, Shiori; Ohmori, Hitoshi; Sasaki, Takamitsu; Miyagawa, Yoshihiro; Kawahara, Isao; Kido, Akira; Tanaka, Yasuhito; Kuniyasu, Hiroki
• Publication, Distribution, etc.: Wiley
• Publication Date: 2022-08
• Publication Date (W3CDTF): 2022-08
• Alternative Title: 酸化型HMGB-1は間葉系幹細胞/間葉系細胞を介して大腸癌の転移性を促進する
• Periodical title: Cancer science
• No. or year of volume/issue: 113 8
• Volume: 113
• Issue: 8
• Pages: 2904-2915
• ISSN (Periodical Title): ISSN : 1347-9032
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2023-03-15
• Dissertation Number: 甲第874号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: cancer metastasis; colorectal cancer; HMGB1; mesenchymal stem cell; stemness
• Target Audience: 一般
• Note (General): type:Thesis; High mobility group box-1 (HMGB1) is known to be a chemotactic factor for mesenchymal stem/stromal cells (MSCs), but the effect of post-translational modification on its function is not clear. In this study, we hypothesized that differences in the oxidation state of HMGB1 would lead to differences in the function of MSCs in cancer. In human colorectal cancer, MSCs infiltrating into the stroma were correlated with liver metastasis and serum HMGB1. In animal models, oxidized HMGB1 mobilized three-fold fewer MSCs to subcutaneous tumors compared with reduced HMGB1. Reduced HMGB1 inhibited the proliferation of mouse bone marrow MSCs (BM-MSCs) and induced differentiation into osteoblasts and vascular pericytes, whereas oxidized HMGB1 promoted proliferation and increased stemness, and no differentiation was observed. When BM-MSCs pretreated with oxidized HMGB1 were co-cultured with syngeneic cancer cells, cell proliferation and stemness of cancer cells were increased, and tumorigenesis and drug resistance were promoted. In contrast, co-culture with reduced HMGB1-pretreated BM-MSCs did not enhance stemness. In an animal orthotopic transplantation colorectal cancer model, oxidized HMGB1, but not reduced HMGB1, promoted liver metastasis with intratumoral MSC chemotaxis. Therefore, oxidized HMGB1 reprograms MSCs and promotes cancer malignancy. The oxidized HMGB1–MSC axis may be an important target for cancer therapy.; 博士（医学）・甲第874号・令和5年3月15日; © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.; identifier:Cancer science Vol.113 No.8 p.2904-2915 (2022 Aug); identifier:13479032; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4106; identifier:Cancer science, 113(8): 2904-2915
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1111/cas.15400
• 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): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4106/1/01%e7%94%b2874%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4106/2/02%e7%94%b2874%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4106/6/03%e7%94%b2874%e6%9c%ac%e6%96%87.pdf fulltext