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

Research Project

Project/Area Number 18K15040
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionTeikyo 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
Project Status Completed (Fiscal Year 2019)
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)
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
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.

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。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] OLFM4 Enhances STAT3 Activation and Promotes Tumor Progression by Inhibiting GRIM19 Expression in Human Hepatocellular Carcinoma2019

    • Author(s)
      Ashizawa Y, Kuboki S, Nojima H, Takano S, Ohtsuka M, et al
    • Journal Title

      Hepatology Communications

      Volume: 3 Issue: 7 Pages: 954

    • DOI

      10.1002/hep4.1361

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Mol Clin Oncol.

      Volume: 10 Pages: 419-424

    • DOI

      10.3892/mco.2019.1807

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of Pin1 as a Key Molecule for EMT Induction by Activation of STAT3 and NF-κB in Human Gallbladder Cancer2019

    • Author(s)
      Nakada S, Kuboki S, Nojima H, Yoshitomi H, Furukawa K, Takayashiki T, Takano S, Miyazaki M, Ohtsuka M.
    • Journal Title

      Ann Surg Oncol.

      Volume: 26 Issue: 3 Pages: 907

    • DOI

      10.1245/s10434-018-07132-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucagonoma with necrolytic migratory erythema: Metabolic profile and detection of biallelic inactivation of DAXX Gene2018

    • 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.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 103 Issue: 7 Pages: 2417

    • DOI

      10.1210/jc.2017-02646

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Surg Case Rep.

      Volume: 4 Issue: 1 Pages: 43-43

    • DOI

      10.1186/s40792-018-0434-3

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 当科における3D腹腔鏡を使用した腹腔鏡下脾動静脈温存尾側膵切除術2019

    • Author(s)
      野島広之 吉富秀幸 古川勝規 高屋敷 吏 久保木 知 高野重紹 鈴木大亮 酒井 望 賀川真吾 三島 敬 宮崎 勝 大塚将之
    • Organizer
      第119回 日本外科学会定期学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Initial results and the effectiveness of laparoscopic hepatectomy2019

    • Author(s)
      H Nojima, , M Ohtsuka
    • Organizer
      2nd World Congress of the International Laparoscopic Liver Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肝門部領域胆管癌での胆道再建を伴う肝葉切除におけるSSIリスク因子の検討2019

    • Author(s)
      野島広之 久保木 知 吉富秀幸 古川勝規 高屋敷 吏 高野重紹 鈴木大亮 酒井 望 賀川真吾 大塚将之
    • Organizer
      第74回日本消化器外科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脾動脈背側アプローチによる腹腔鏡下尾側膵切除術の有用性2019

    • Author(s)
      野島広之 清水宏明 幸田圭史 吉富秀幸 古川勝規 高屋敷 吏 久保木 知 高野重紹 大塚将之
    • Organizer
      第11回膵臓内視鏡外科研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 胃癌肝転移に対する適切な手術適応、予後予測因子としてのmodified Glasgow prognostic score (mGPS)の有用性の検討2018

    • Author(s)
      野島広之 久保木 知 吉富秀幸 古川勝規 高屋敷 吏 高野重紹 鈴木大亮 酒井 望 賀川真吾 佐藤豊 宮崎 勝 大塚将之
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Research-status Report
  • [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
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 80歳以上の超高齢者に対する肝切除術での術後合併症とリスク因子の検討2018

    • Author(s)
      野島広之 吉富秀幸 古川勝規 高屋敷 吏 久保木 知 高野重紹 鈴木大亮 酒井 望 宮崎 勝 大塚将之
    • Organizer
      第73回日本消化器外科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肝細胞癌におけるスフィンゴシン1リン酸レセプターの発現についての検討2018

    • Author(s)
      横田哲生 野島広之 久保木 知 吉富秀幸 古川勝規 高屋敷 吏 高野重紹 鈴木大亮 酒井 望 賀川真吾 佐藤豊 宮崎 勝 大塚将之
    • Organizer
      第16回 日本消化器外科学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 局所進行膵癌に対する門脈合併切除再建の意義2018

    • Author(s)
      野島広之,高野重紹,吉富秀幸,古川勝規,高屋敷吏,久保木知, 鈴木大亮,酒井望,賀川真吾,三島敬,中台英里,大塚将之
    • Organizer
      第80回日本臨床外科学会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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