2022 Fiscal Year Final Research Report
Elucidation of the mechanism of Fe ion regulation of cancer microenvironment by tumor vascular endothelial cells
| Project/Area Number |
21K15531
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | がん微小環境 / 腫瘍血管 / 生体イメージング / 鉄イオン / セルロプラスミン / 膠芽腫 / 血管内皮細胞 |
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| Outline of Final Research Achievements |
This study aimed to elucidate the microenvironmental mechanisms by which tumor vascular endothelial cells produce ceruloplasmin and confer anticancer drug resistance through modulation of iron ion metabolism in cancer.
Vascular endothelial cell-specific ceruloplasmin is responsible for the redox reaction of iron ions in the tumor environment and promotes iron ion uptake into cancer cells. Iron ions act as a cofactor for DNA demethyltransferases in the nucleus of cancer cells, causing epigenetic changes in the genome of cancer cells and induction of anticancer drug-resistant genes. This microenvironment-forming mechanism was also found to act in glioblastoma and melanoma, which have poor prognosis, and has the potential to be applied to the development of treatment for various malignant tumors.
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| Free Research Field |
腫瘍生物学
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| Academic Significance and Societal Importance of the Research Achievements |
VEGFシグナルを標的とした抗腫瘍血管療法が有効ではない腫瘍は多く、新規治療法の開発が望まれている。本研究成果である血管内皮細胞による鉄代謝を介したがん微小環境制御機構は、これまでの考えられてきた血管内皮細胞が持つ病理学的な学術的意義を広める成果であると言える。またこのメカニズムは幅広い癌種で作用することが明らかとなった。内皮細胞による、鉄イオン代謝を介したがん細胞ゲノムのエピジェネティック制御は抗癌剤耐性化に重要であることから、既存のがん治療法への上乗せ期待できる多くのがん治療に適用しうる薬剤の開発につながると期待される。
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