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Research Paper|Volume 13, Issue 19|pp 23393—23406

Cosmc transfection decreases malignant behavior of Tn+ cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure

Ruisong Ding1, Xingyou Hu2, Wen Hu1, Zhenzhen Du1, Panpan Huang1, Mengyang Wang1, Jiaoyue Sheng4, Yanchao Ma1, Ailing Wang3, Xiying Luan1, Menghua Dong1, Qizhi Cao1, Yanfen Zou5, Tao Hu1
  • 1Department of Immunology, Binzhou Medical University, Yantai 264003, PR China
  • 2Qingdao University, Qingdao 266071, PR China
  • 3Laboratory Department, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province 264100, PR China
  • 4Department of Oncology, Qingdao No.6 People’s Hospital, Qingdao 266033, PR China
  • 5Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, PR China
* Equal contribution
Received: July 21, 2021Accepted: September 28, 2021Published: October 13, 2021
https://doi.org/10.18632/aging.203633

Copyright: © 2021 Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cosmc mutations may cause abnormal O-glycosylation and result in Tn antigen expression. In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased. Core 1-, 2-, and 3-derived O-glycans were absent in Tn+ cells. After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity. Core 2-derived O-glycans appeared in transfected LS174T-Tn+ cells, and their structural types and levels were lower than those in LS174T-Tn− cells. Core 3-derived O-glycans were present only in LS174T-Tn− cells. The activity of C3GnT in LS174T-Tn+ cells was lower than that in LS174T-Tn− cells, and it was absent in Jurkat T cells. Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells. The results demonstrated that the composition and structure of O-glycans were different among various Tn+ cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli. Thus, Cosmc transfection may effectively decrease the malignant behavior of Tn+ tumor cells and enhance their sensitivity to apoptosis when induced by Apo2L/TRAIL through modification of O-glycans.