analysis of immune factor in choriocarcinoma microenvironment

• Project/Area Number: 17K16845
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: Niimi Kaoru 名古屋大学, 医学部附属病院, 病院講師 (20571334)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 絨毛癌 / 絨毛性腫瘍 / C2GnT / 糖転移酵素 / hCG / NK細胞 / 糖鎖 / 化学療法耐性株 / CGｎT / 抗癌剤

Outline of Final Research Achievements

We investigated C2GnT expression in gestational trophoblastic diseases. We established C2GnT knockout (KO) cells with Jar and BeWo cells and investigated cytotoxicity of NK cells against those cells. MICA and MUC1 glycosylation were analyzed by immunoprecipitation. We incubated C2GnT-KO and control with TRAIL and cell viability were analyzed. We inoculated the C2GnT-KO and control cells subcutaneously into nude mice. C2GnT was highly expressed in trophoblasts of choriocarcinoma but not in hydatidiform mole and normal placenta. C2GnT-KO cells were more efficiently killed by NK cells than controls. Sugar chains attached by C2GnT on MICA and MUC1 in C2GnT-KO cells were significantly decreased. The cell viability of C2GnT-KO cells were lower than controls depending on TRAIL amount. C2GnT-KO promoted longer survival as compared with the controls. Choriocarcinoma cells may acquire a high malignant potential by expressing C2GnT with glycosylation to MICA and MUC1.

Academic Significance and Societal Importance of the Research Achievements

糖転移酵素C2GnTは、絨毛癌細胞で高発現しており、MICA及びMUC1の糖鎖修飾を介して、NK細胞の免疫システムから逃避し、高い悪性能を有する可能性が示唆された。本研究は、絨毛性腫瘍患者を対象とした新規治療法として、C2GnTの発現抑制にNK細胞に関連した免疫治療を加えることの有効性を、細胞生物学的に解析したものである。今後in vivoでの解析をさらに進めることで、臨床応用の可能性が期待できると考える。

Research Products

• [Presentation] 絨毛性疾患の疫学、診断、治療 (2019)
  • Author(s): 新美 薫
  • Organizer: 第71回日本産科婦人科学会学術講演会
  • Invited
• [Presentation] 絨毛癌細胞のNK細胞免疫逃避機構における糖転移酵素C2GnTの役割 (2019)
  • Author(s): 新美薫、山本英子、中村謙一、田口結加里、渡邉絵里、西野公博、吉川史隆
  • Organizer: 第27回日本胎盤学会学術集会
• [Presentation] 絨毛癌細胞におけるNK 細胞を介した免疫避機構に対する糖転移酵素C2GnT の役割 (2018)
  • Author(s): 中村謙一，池田芳紀，西野公博，新美 薫，山本英子，吉川史隆
  • Organizer: 第70 回日本産科婦人科学会学術講演会
• [Presentation] 日本におけるPSTT及びETTの臨床的特徴 (2018)
  • Author(s): 新美 薫，中村謙一，池田芳紀，西野公博，山本英子，吉川史隆
  • Organizer: 第70 回日本産科婦人科学会学術講演会
• [Presentation] Clinial chracteristic of PSTT and ETT in Japan (2018)
  • Author(s): Niimi K, Yamamoto E, Nishino K, Nakamura K, Ikeda Y, Kikkawa F
  • Organizer: 17th biennial meeting of the international gyenecologic cancer society（IGCS2018）
  • Int'l Joint Research
• [Presentation] Glycosyltransferase regulate of malignant potential of trophoblast (2018)
  • Author(s): Niimi K, Yamamoto E, Nakamura L, Nishino K, Kikkawa F
  • Organizer: IFPA 2018 Tokyo
  • Int'l Joint Research
• [Presentation] Role of core 2β 1, 6-N acetylglcosaminyl transferase in evasion mechanism through NK cell (2018)
  • Author(s): Nakamura K, Niimi K, Ikeda Y, Nishino K, Yamamoto E, Kikkawa F
  • Organizer: IFPA 2018 Tokyo
  • Int'l Joint Research
• [Book] 基礎と臨床の両側面からみた胎盤学,15絨毛性腫瘍とhCGの糖鎖修飾 (2019)
  • Author(s): 日本胎盤学会
  • Total Pages: 448
  • Publisher: メジカルビュー社
  • ISBN: 9784758317627