Sphingosine-1-phosphate receptor-1 promotes vascular invasion and EMT in hepatocellular carcinoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15040
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Teikyo University (2019); Chiba University (2018)
• Principal Investigator: NOJIMA HIROYUKI 帝京大学, 医学部, 講師 (10507320)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 進行肝細胞癌 / スフィンゴシン1リン酸 / EMT / cancer stemness

Outline of Final Research Achievements

Among patients with HCC, the high S1PR1 expression group had significantly shorter overall survival (OS) than the low S1PR1 expression group. Moreover, high S1PR1 expression levels were significantly associated with shorter recurrence-free survival (RFS), and increased risk for portal and hepatic vein invasion and intrahepatic metastasis. Moreover, these patients had significantly shorter OS and RFS irrespective of the expression of S1PR3. Multivariate analyses revealed that S1PR1 overexpression was an independent prognostic factor in HCC patients. S1PR1 overexpression positively correlated with vimentin and MMP-9 expression, and negatively correlated with E-cadherin. Additionally, S1PR1 overexpression induced EMT and enhanced tumor invasion and cancer stemness. These results indicate the potential of S1PR1 to serve as a therapeutic target for HCC patients with vascular invasion.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

進行肝細胞癌は未だ予後不良であり、特に血管浸潤を有する場合は肝内転移や術後早期の再発をしばしば認める。血管浸潤や転移にはepithelial-mesenchymal transition (EMT)、cancer stemnessの関与が示唆されている。S1PR1がEMTを促進しcancer stemnessを誘導していることが示唆された。S1PR1がEMTやcancer stemnessの誘導しており、同レセプターの制御が肝細胞癌における新たな治療となりうる可能性を示した。