Nakamura Kenichi, Niimi Kaoru, Yamamoto Eiko, Ikeda Yoshiki, Nishino Kimihiro, Suzuki Shiro, Kajiyama Hiroaki, Kikkawa Fumitaka
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Biochem Biophys Rep. 2021 Feb 13;26:100951. doi: 10.1016/j.bbrep.2021.100951. eCollection 2021 Jul.
Hyperglycosylated human chorionic gonadotropin (H-hCG) is secreted from choriocarcinoma and contains a core2 -glycan formed by core2 β1,6-N-acetylglucosaminyl transferase (C2GnT). Choriocarcinoma is considered immunogenic as it is gestational and contains paternal chromosomal components. Here we examined the function of C2GnT in the evasion of choriocarcinoma cells from natural killer (NK) cell-mediating killing. We determined that C2GnT is highly expressed in malignant gestational trophoblastic neoplasms. C2GnT KO downregulates core2 -glycan expression in choriocarcinoma cells, which are more efficiently killed by NK cells than control cells. C2GnT KO cell containing tumor necrosis factor-related apoptosis inducing ligand have lower viability than control cells. Additionally, poly--acetyllactosamine in core2 branched oligosaccharides on MHC class I-related chain A (MICA) and mucin1 (MUC1) is significantly reduced in C2GnT KO cells. Meanwhile, the cumulative survival rate of nude mice inoculated with C2GnT KO tumors was higher than that of the control group. These findings suggest that choriocarcinoma cells may escape NK cell-mediated killing via glycosylation of MICA and MUC1.
高糖基化人绒毛膜促性腺激素（H-hCG）由绒毛膜癌分泌，含有由核心2β1,6-N-乙酰氨基葡萄糖转移酶（C2GnT）形成的核心2聚糖。绒毛膜癌被认为具有免疫原性，因为它是妊娠性的，并且含有父系染色体成分。在这里，我们研究了C2GnT在绒毛膜癌细胞逃避自然杀伤（NK）细胞介导的杀伤中的作用。我们确定C2GnT在恶性妊娠滋养细胞肿瘤中高表达。C2GnT基因敲除下调了绒毛膜癌细胞中核心2聚糖的表达，与对照细胞相比，这些细胞被NK细胞杀伤的效率更高。含有肿瘤坏死因子相关凋亡诱导配体的C2GnT基因敲除细胞的活力低于对照细胞。此外，C2GnT基因敲除细胞中与MHC I类相关链A（MICA）和粘蛋白1（MUC1）上核心2分支寡糖中的聚乙酰乳糖胺显著减少。同时，接种C2GnT基因敲除肿瘤的裸鼠的累积存活率高于对照组。这些发现表明，绒毛膜癌细胞可能通过MICA和MUC1的糖基化逃避NK细胞介导的杀伤。
