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

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 i...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357642/
https://www.ncbi.nlm.nih.gov/pubmed/35570394
http://dx.doi.org/10.1111/cas.15400
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author 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_facet 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_sort Kishi, Shingo
collection PubMed
description 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.
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spelling pubmed-93576422022-08-09 Oxidized high mobility group B‐1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells 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 Cancer Sci Original Articles 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. John Wiley and Sons Inc. 2022-05-23 2022-08 /pmc/articles/PMC9357642/ /pubmed/35570394 http://dx.doi.org/10.1111/cas.15400 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) 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.
spellingShingle Original Articles
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
Oxidized high mobility group B‐1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells
title Oxidized high mobility group B‐1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells
title_full Oxidized high mobility group B‐1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells
title_fullStr Oxidized high mobility group B‐1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells
title_full_unstemmed Oxidized high mobility group B‐1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells
title_short Oxidized high mobility group B‐1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells
title_sort oxidized high mobility group b‐1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357642/
https://www.ncbi.nlm.nih.gov/pubmed/35570394
http://dx.doi.org/10.1111/cas.15400
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