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
Note (General)type:Thesis
High mobility group box-1(HMGB1) is known to be a chemotactic factor for mesenchymalstem/stromal cells (MSCs), but the effect of post-translationalmodification onits function is not clear. In this study, we hypothesized that differences in the oxidationstate of HMGB1 would lead to differences in the function of MSCs in cancer. Inhuman colorectal cancer, MSCs infiltrating into the stroma were correlated with livermetastasis and serum HMGB1. In animal models, oxidized HMGB1 mobilized three-foldfewer MSCs to subcutaneous tumors compared with reduced HMGB1. ReducedHMGB1 inhibited the proliferation of mouse bone marrow MSCs (BM-MSCs)andinduced differentiation into osteoblasts and vascular pericytes, whereas oxidizedHMGB1 promoted proliferation and increased stemness, and no differentiation wasobserved. When BM-MSCspretreated with oxidized HMGB1 were co-culturedwithsyngeneic cancer cells, cell proliferation and stemness of cancer cells were increased,and tumorigenesis and drug resistance were promoted. In contrast, co-culturewithreduced HMGB1-pretreatedBM-MSCsdid not enhance stemness. In an animal orthotopictransplantation colorectal cancer model, oxidized HMGB1, but not reducedHMGB1, promoted liver metastasis with intratumoral MSC chemotaxis. Therefore,oxidized HMGB1 reprograms MSCs and promotes cancer malignancy. The oxidizedHMGB1–MSCaxis 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
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2023-12-05T21:41:07+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション