analysis of immune factor in choriocarcinoma microenvironment

2019 Fiscal Year Final Research Report

• 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
• Keywords: 絨毛癌 / 絨毛性腫瘍 / C2GnT / 糖転移酵素 / hCG / NK細胞

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.

Free Research Field

絨毛性疾患

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。