| Project/Area Number |
15H04925
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高屋敷 吏 千葉大学, 大学院医学研究院, 講師 (30456024)
吉富 秀幸 千葉大学, 大学院医学研究院, 准教授 (60375631)
宮崎 勝 国際医療福祉大学, 大学病院, 教授 (70166156)
酒井 望 千葉大学, 医学部附属病院, 助教 (70436385)
賀川 真吾 千葉大学, 医学部附属病院, 助教 (90507302)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
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| Keywords | 膵癌 / Prrx1 / Metadherin / 中和抗体 / Epithelial plasticity / EMT / MET / 転移 / 膵臓外科学 / 浸潤・転移 / 浸潤、転移 |
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| Outline of Final Research Achievements |
Epithelial-mesenchymal transition (EMT) is believed to be important for primary tumor progression and dissemination, whereas mesenchymal-epithelial transition (MET) appears crucial for metastatic colonization. We described novel roles for two Prrx1 isoforms in the metastatic cascade using in vitro and in vivo models of PDAC. Prrx1b promotes invasion and EMT, whereas Prrx1a stimulates metastatic outgrowth in the liver and MET. We further demonstrate that the switch from Prrx1b to Prrx1a governs EMT plasticity both in mouse models of PDAC as well as in human PDAC. Lastly, we identify hepatocyte growth factor (HGF) as a novel transcriptional target of Prrx1b. Targeted therapy of HGF in combination with gemcitabine in a preclinical model of PDAC eliminates metastatic disease. We provide new insights into the isoform-specific roles of Prrx1a and Prrx1b in primary PDAC formation, dissemination and metastatic colonization, allowing for novel therapeutic strategies targeting EMT plasticity.
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