Sphingosine-1-phosphate receptor-1 promotes vascular invasion and EMT in hepatocellular carcinoma
| Project/Area Number |
18K15040
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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 48040:Medical biochemistry-related
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| Research Institution | Teikyo University (2019)
Chiba University (2018) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 進行肝細胞癌 / スフィンゴシン1リン酸 / EMT / cancer stemness / スフィンゴシン1-リン酸（S1P） / S1Pレセプター / スフィンゴシン1－リン酸（S1P） / S1P受容体 / 上皮間葉転換 |
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| 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.
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| 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。
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] Successful treatment of a locally advanced unresectable pancreatic cancer patient with interstitial pneumonitis by conversion surgery following gemcitabine plus nab-paclitaxel chemotherapy: A case report.2019
Author(s)
Yokota T, Takano S, Yoshitomi H, Kagawa S, Furukawa K, Takayashiki T, Kuboki S, Suzuki D, Sakai N, Nojima H, Mishima T, Nakadai E, Ohtsuka M.
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Journal Title
Mol Clin Oncol.
Volume: 10
Pages: 419-424
DOI
Related Report
Peer Reviewed
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[Journal Article] Glucagonoma with necrolytic migratory erythema: metabolic profile and detection of biallelic inactivation of DAXX gene.2018
Author(s)
①Tamura A, Ogasawara T, Fujii Y, Kaneko H, Nakayama A, Higuchi S, Hashimoto N, Miyabayashi Y, Fujimoto M, Komai E, Kono T, Sakuma I, Nagano H, Suzuki S, Koide H, Yokote K, Iseki K, Oguma R, Matsue H, Nojima H, Sugiura K, Yoshitomi H, Ohtsuka M, Rahmutulla B, Kaneda A, Inoshita N, Ogawa S, Tanaka T.
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Journal Title
J Clin Endocrinol Metab.
Volume: 23
Issue: 7
Pages: 1-4
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Novel treatment strategy with radiofrequency ablation and surgery for pregnant patients with hepatocellular carcinoma: a case report.2018
Author(s)
Matsuo M, Furukawa K, Shimizu H, Yoshitomi H, Takayashiki T, Kuboki S, Takano S, Suzuki D, Sakai N, Kagawa S, Nojima H, Ohsuka M.
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Journal Title
Surg Case Rep.
Volume: 4
Issue: 1
Pages: 43-43
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Risk factors for postoperative complications after hepatectomy in super-elderly patients2018
Author(s)
H Nojima, H Yoshitomi, K Furukawa, T Takayashiki, S Kuboki, S Takano, D Suzuki, N Sakai, S Kagawa T Mishima, M Miyazaki, M Ohtsuka
Organizer
第30回日本肝胆膵外科学会・学術集会
Related Report
Int'l Joint Research
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