2021 Fiscal Year Final Research Report
Upregulation of mobility in pancreastic cancer cells by secreted S100A11 through activation of surrounding fibroblasts.
| Project/Area Number |
19K16714
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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 | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | S100A11 / RAGE / 間質線維芽細胞 / 線維化 |
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| Outline of Final Research Achievements |
In this study, we investigated the extracellular role of S100A11 in crosstalking between pancreatic ductal adenocarcinoma (PDAC) cells and surrounding fibroblasts in PDAC progression.
An abundant S100A11 promoted stromal fibroblast proliferation by activating downstream p70S6kinase through RAGE. Furthermore, activation of TPL2 in stromal fibroblasts led to secretion of PEG2, which enhanced invasion and metastasis of cancer cells. These results indicate that a novel role of the secretory S100A11 in PDAC disseminative progression through activation of surrounding fibroblasts triggered by the S100A11-RAGE-TPL2-COX2 pathway. These findings will contribute to therapeutic target to suppress PDAC progression through preventing PDAC-associated fibroblast proliferation.
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| Free Research Field |
分子細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
がんの増殖・浸潤・転移には多くの要因が関係しており、近年ではがん周囲の間質細胞が積極的に関与することが報告されている。特に膵臓がんでは間質細胞の増加を伴う事で治療が難しくなるなどの影響も見られ、間質細胞とがんの関係を明らかにすることはがんの病態解明、新たな治療方法の開発を目指す上でも重要である。
本研究により、膵臓がん細胞から分泌されるS100A11はRAGEを介してがん周囲の間質線維芽細胞に作用してその増殖を促進させること、またPEG2を分泌することでがん細胞の浸潤・転移を促進させることが明らかとなった。これら知見ががん微小環境内コミュニケーションへのより深い理解へと繋がることが期待される。
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