2022 Fiscal Year Final Research Report
Investigation of activation mechanisms and exploration of inhibition therapy of HGF-MET signal in cancer microenvironment
| Project/Area Number |
20K16175
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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 49020:Human pathology-related
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | MET / HGF / がん周囲微小環境 / 分子標的薬 |
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| Outline of Final Research Achievements |
We analyzed the significance and inhibitory therapy of the HGF-dependent MET activation signaling, which consists of the stromal-derived hepatocyte growth factor (HGF) and its receptor MET on cancer cells. We showed that HGF-dependent MET signaling is regulated by hepatocyte growth factor inhibitor-1 (HAI-1), and that decreased expression of HAI-1 enhanced MET-mediated cell proliferation. Synthetic HGF activation inhibitors with functions similar to HAI-1 increased necrotic areas in tumors with reduced HAI-1 expression. The results suggest the usefulness of synthetic HGF activation inhibitors.
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| Free Research Field |
人体病理学
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| Academic Significance and Societal Importance of the Research Achievements |
HGF 依存性 MET 活性化の制御は，転移性腫瘍や抗がん剤耐性を獲得した腫瘍に対して，新たな治療選択肢を提供しうる．本研究では，HGF-MET シグナルが亢進している一部の腫瘍において，合成 HGF 活性化阻害剤が治療効果を発揮することが実験動物レベルで示唆された．今後の研究の進展により，合成 HGF 活性化阻害剤の臨床応用が期待できる．
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