Analysis of the mechanism of enhancement of metastasis by pathogenic mitochondrial DNA mutation.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07654
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: TAKENAGA Keizo 千葉県がんセンター(研究所), がん先進治療開発研究室, 特任研究員 (80260256)
• Co-Investigator(Kenkyū-buntansha): 越川 信子 千葉県がんセンター(研究所), がん遺伝創薬研究室, 主任上席研究員 (90260249)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: ミトコンドリアDNA / 細胞外小胞 / 細胞間移行 / 転移 / トンネルナノチューブ

Outline of Final Research Achievements

Mitochondria containing metastasis-enhancing pathogenic mtDNA in mouse high-metastatic lung tumor cells were transferred to low-metastatic cells and stromal cells via extracellular vesicles (EVs) in vitro and in the tumor microenvironment. Among the subpopulations of EVs, the small-EV fraction contained mutant mtDNA and mitochondrial proteins. On the other hand, co-culture of human mtDNA deficient ρ０cells with a human cancer cell line with mtDNA mutations resulted in the appearance of a small number of ρ０cell colonies with increased copy number of the said mutant mtDNA. Some of the ρ０cells, depending on the nature of the transferred mtDNA mutations, showed enhanced cell motility. These results infer an enhancement of metastatic potential by mutant mtDNA intercellular transfer during tumor progression.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

細胞外小胞を介した転移促進性変異mtDNAの低転移性細胞への伝搬は、低転移性細胞に高転移性を賦与する可能性があり、創薬、治療、転移予測の面から様々な展開を促す可能性がある。