1. Academic Validation
  2. Oxidative High Mobility Group Box-1 Accelerates Mitochondrial Transfer from Mesenchymal Stem Cells to Colorectal Cancer Cells Providing Cancer Cell Stemness

Oxidative High Mobility Group Box-1 Accelerates Mitochondrial Transfer from Mesenchymal Stem Cells to Colorectal Cancer Cells Providing Cancer Cell Stemness

  • Int J Mol Sci. 2025 Jan 30;26(3):1192. doi: 10.3390/ijms26031192.
Rika Sasaki 1 Yi Luo 1 Shingo Kishi 1 2 Ruiko Ogata 1 Yukiko Nishiguchi 1 Takamitsu Sasaki 1 Hitoshi Ohmori 1 Rina Fujiwara-Tani 1 Hiroki Kuniyasu 1
Affiliations

Affiliations

  • 1 Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan.
  • 2 Pathology Laboratory, Research Institute, Tokushukai Nozaki Hospital, 2-10-50 Tanigawa, Daito 574-0074, Osaka, Japan.
Abstract

Mitochondria are important organelles for cell metabolism and tissue survival. Their cell-to-cell transfer is important for the fate of recipient cells. Recently, bone marrow mesenchymal stem cells (BM-MSCs) have been reported to provide mitochondria to Cancer cells and rescue mitochondrial dysfunction in Cancer cells. However, the details of the mechanism have not yet been fully elucidated. In this study, we investigated the humoral factors inducing mitochondrial transfer (MT) and the mechanisms. BM-MSCs produced MT in colorectal Cancer (CRC) cells damaged by 5-fluorouracil (5-FU), but were suppressed by the anti-high mobility group box-1 (HMGB1) antibody. BM-MSCs treated with oxidized HMGB1 had increased expression of MT-associated genes, whereas reduced HMGB1 did not. Inhibition of nuclear factor-κB, a downstream factor of HMGB1 signaling, significantly decreased MT-associated gene expression. CRC cells showed increased stemness and decreased 5-FU sensitivity in correlation with MT levels. In a mouse subcutaneous tumor model of CRC, 5-FU sensitivity decreased and stemness increased by the MT from host mouse BM-MSCs. These results suggest that oxidized HMGB1 induces MTs from MSCs to CRC cells and promotes Cancer cell stemness. Targeting of oxidized HMGB1 may attenuate stemness of CRCs.

Keywords

NF–κB; cancer stemness; chemoresistance; colorectal cancer; mitochondrial transfer; oxidized HMGB1.

Figures
Products