2018 Fiscal Year Final Research Report
Effect of acidic extracellular pH on reprogramming of glycolysis -special reference to maintenance of cancer stem cell-
| Project/Area Number |
16K11517
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Ohu University |
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Principal Investigator |
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| Research Collaborator |
MAEDA Toyonobu 奥羽大学, 歯学部, 准教授 (10382756)
SUZUKI Atsuko 奥羽大学, 歯学部, 講師 (90405986)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 酸性細胞外pH |
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| Outline of Final Research Achievements |
Extracellular pH (pHe) of tumor tissue is often acidic. In this study, we identified TRPM5 as a molecule contributing acidic pHe sensing. We also found that 5-year survival rate of patients with melanoma and gastric cancer were short. When acidic pHe-adapted cells were established rom NR-S1 and Lewis lung cell carcinoma, tumorigenesis in NR-S1 model and lung metastasis in Lewis lung carcinoma mode were significantly elevated. These phenotypes were maintained even though they were passaged around 10 times at neutral pHe.
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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 |
これまで、がん細胞の性質として、グルコース代謝においては解糖系に依存したエネルギー産生が旺盛であるため、乳酸を最終代謝産物として分泌し、結果としてがん組織内の細胞外pHは低下するという結果論的な認識であったが、私たちの結果は、酸性細胞外pHが糖代謝を制御し、さらにがんの再発に関与する造腫瘍性や遠隔転移能を亢進させることが明かとなり、さらに、酸性pHeの受容機構を阻害することで、抗転移療法の臨床応用の可能性を示したことは、新たな治療概念を構築する基礎データとして意義深い。
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