roles of ceramide in ovarian cancer

• Project/Area Number: 16K11125
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Setsunan University (2018); Tohoku University (2016-2017)
• Principal Investigator: kazuyuki kitatani 摂南大学, 薬学部, 講師 (40539235)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: セラミド / セラミド合成酵素 / 転移 / 細胞運動性 / 卵巣がん / 卵巣癌 / 運動能 / がん転移

Outline of Final Research Achievements

Ceramide has been emerging as a bioactive lipid that regulate metastatic potential in ovarian cancer. However, whether ceramide contents and metabolism are dysregulated remained unknown. In the present study, I established highly metastatic ovarian cancer cells with ceramide synthesis and identified ceramide-generating enzyme responsible for suppressing cell motility and metastatic potential of ovarian cancer.

Academic Significance and Societal Importance of the Research Achievements

セラミドはがん細胞において細胞増殖や運動性を抑える生物活性を有しており，抗転移性脂質であると予測されている．マウス卵巣がんモデルを用いた当研究により，セラミド合成酵素2（CerS2）発現低下およびセラミド量減少が高い転移性を有する卵巣がん細胞の特徴であることを見出した．さらに，CerS2発現をノックダウンすることで，卵巣がん細胞の転移能が低下することを明らかにした．これらの研究成果は，卵巣がん転移におけるセラミドおよび生成酵素の臨床的意義を明らかにするための基盤構築に資すると期待される．さらに，これらの分子生物学的な特徴を活用し，新たながん転移のバイオマーカーの開発が見込まれる．

Research Products

• [Int'l Joint Research] Stony Brook University/Virginia University(米国)
• [Int'l Joint Research] University of Virginia/Department of Pharmacology(米国)
• [Journal Article] La-Related Protein 4 as a Suppressor for Motility of Ovarian Cancer Cells (2019)
  • Author(s): Egiz M, Usui T, Ishibashi M, Zhang X, Shigeta S, Toyoshima M, Kitatani K, Yaegashi N
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 247 Issue: 1 Pages: 59-67
  • DOI: 10.1620/tjem.247.59
  • NAID: 130007556949
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Regulation of necroptosis by lipids (2018)
  • Author(s): 張雪薇 北谷和之
  • Journal Title: 生化学 Volume: 90 Issue: 6 Pages: 797-800
  • DOI: 10.14952/SEIKAGAKU.2018.900797
  • NAID: 40021783121
  • ISSN: 0037-1017
  • Year and Date: 2018-12-25
• [Journal Article] Tyrosine kinase receptor TIE-1 mediates platinum resistance by promoting nucleotide excision repair in ovarian cancer. (2018)
  • Author(s): Ishibashi M, Toyoshima M, Zhang X, Hasegawa-Minato J, Shigeta S, Usui T, Kemp CJ, Grandori C, Kitatani K, Yaegashi N
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 13207-13207
  • DOI: 10.1038/s41598-018-31069-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ceramide nanoliposomes as a MLKL-1-dependent, necroptosis-inducing, chemotherapeutic reagent in ovarian cancer (2018)
  • Author(s): Xuewei Zhang, Kazuyuki Kitatani, Masafumi Toyoshima, Masumi Ishibashi, Toshinori Usui, Junko Minato, Mahy Egiz, Shogo Shigeta, Todd Fox, Tye Deering, Mark Kester, Nobuo Yaegashi
  • Journal Title: Molecular Cancer Therapeutics Volume: 17 Issue: 1 Pages: 50-59
  • DOI: 10.1158/1535-7163.mct-17-0173
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] セラミド合成酵素による癌転移制御 (2016)
  • Author(s): 北谷和之、張 雪薇、臼井利典、豊島将文、重田昌吾、Mahy Egiz、湊 純子、石橋ますみ、小木曽英夫、岡崎俊朗、八重樫伸生
  • Journal Title: 脂質生化学研究 Volume: 58 Pages: 182-182
• [Journal Article] 卵巣がん細胞に対するセラミドナノリポソームの抗腫瘍効果 －ネクロプト―シスの誘導ー (2016)
  • Author(s): 張 雪薇、豊島将文、石橋ますみ、臼井利典、湊 純子、重田昌吾、Mark Kester、北谷和之、八重樫伸生
  • Journal Title: 脂質生化学研究 Volume: 58 Pages: 68-69
  • Int'l Joint Research
• [Presentation] The mechanism of ceramide nanoliposomes-induced necroptosis in ovarian cancer (2018)
  • Author(s): Xuewei Zhang, Kazuyuki Kitatani, Masafumi Toyoshima, Masumi Ishibashi, Shogo Shigeta, Junko Minato, Nobuo Yaegashi
  • Organizer: 第70回日本産科婦人科学会・学術集会
  • Int'l Joint Research
• [Presentation] Role of RNA chaperones in ovarian cancer metastasis (2018)
  • Author(s): Mahy Egiz, Kazuyuki Kitatani, Masafumi Toyoshima, Masumi Ishibashi, Shogo Shigeta, Junko Minato, Nobuo Yaegashi
  • Organizer: 第70回日本産科婦人科学会・学術集会
  • Int'l Joint Research
• [Presentation] セラミド製剤によるネクロプトーシス誘導 (2018)
  • Author(s): 北谷和之、張雪 薇、石橋ますみ、豊島將文、松田将也、八重樫伸生、奈邉 健
  • Organizer: 第68回日本薬学会 近畿支部
• [Presentation] リポソーム化セラミドの抗腫瘍活性：プログラム化ネクローシスの誘 (2018)
  • Author(s): 北谷和之，張 雪薇，松田将也，Mark Kester，八重樫伸生，奈邉 健
  • Organizer: 第134回日本薬理学会 近畿部会
• [Presentation] 第１３回スフィンゴテラピ研究会 (2018)
  • Author(s): 北谷和之，張 雪薇，松田将也，山本雄大，Mark Kester，八重樫伸生，奈邉 健
  • Organizer: スフィンゴ脂質とプログラム化ネクローシス（ネクロプトーシス）
• [Presentation] Ceramide synthase 2-ceramide axis limits metastatic potential of ovarian cancer (2017)
  • Author(s): Kitatani K
  • Organizer: 15th International Ceramide Conference
  • Int'l Joint Research
• [Presentation] Potential of ceramide nanoliposomes as necroptosis-inducing chemotherapeutic reagents in ovarian cancer (2017)
  • Author(s): Zhang X, Kitatani K, Toyoshima M, Ishibashi M, Usui T, Minato J, Egiz M, Shigeta S, Fox T, Deering T, Kester M, Yaegashi N
  • Organizer: 15th International Ceramide Conference
  • Int'l Joint Research
• [Presentation] セラミド合成酵素２による癌転移制御への関与 (2016)
  • Author(s): 北谷和之、張 雪薇、臼井利典、豊島将文、重田昌吾、Mahy Egiz、湊 純子、石橋ますみ、小木曽英夫、岡崎俊朗、八重樫伸生
  • Organizer: 日本生化学会
  • Place of Presentation: 仙台国際センター／東北大学川内キャンパス（宮城県・仙台市）
  • Year and Date: 2016-09-25