並列タイトル等酸化型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
一般注記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
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
提供元機関・データベース奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU