The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn

被引:4
作者
Ho, Chia-Wen [1 ,4 ]
Lin, Chi-Yu [2 ]
Liaw, Yi-Wei [2 ,3 ]
Chiang, Hsiao-Ling [2 ]
Chin, Yu-Tang [4 ]
Huang, Rui-Lan [5 ]
Lai, Hung-Cheng [5 ,6 ,7 ]
Hsu, Yaw-Wen [6 ]
Kuo, Po-Jan [8 ,9 ]
Chen, Chiao-En [4 ]
Lin, Hung-Yan [4 ]
Whang-Peng, Jacqueline [4 ]
Nieh, Shin [6 ,9 ,10 ]
Fu, Earl [6 ,8 ,9 ]
Liu, Leroy F. [1 ,4 ]
Hwang, Jaulang [1 ,2 ,3 ,6 ]
机构
[1] Taipei Med Univ, Ctr Canc Res, Taipei, Taiwan
[2] Taipei Med Univ, Dept Biochem, Coll Med, Taipei, Taiwan
[3] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei, Taiwan
[4] Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery, Coll Med Sci & Technol, Taipei, Taiwan
[5] Taipei Med Univ, Shuang Ho Hosp, Dept Obstet & Gynecol, New Taipei, Taiwan
[6] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan
[7] Taipei Med Univ, Sch Med, Dept Obstet & Gynecol, Coll Med, Taipei, Taiwan
[8] Natl Def Med Ctr, Dept Periodontol, Sch Dent, Taipei, Taiwan
[9] Triserv Gen Hosp, Taipei, Taiwan
[10] Natl Def Med Ctr, Dept Pathol, Taipei, Taiwan
关键词
Tn antigen; tumor-associated carbohydrate; cytokines; cosmc; hypermethylation; NF-KAPPA-B; SQUAMOUS-CELL CARCINOMA; O-GLYCOSYLATION; CANCER-CELLS; CONSTITUTIVE ACTIVATION; PANCREATIC-CANCER; CHAPERONE COSMC; BREAST-CANCER; EXPRESSION; METASTASIS;
D O I
10.18632/oncotarget.11324
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tn antigen (GalNAc-beta-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. There are also reports that Tn is elevated in inflammatory tissues. However, the molecular mechanism for its elevated levels in cancer and inflammation is unclear. In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. We showed that the Tn level is elevated by the conditioned media of Hras(G12V)-transformed-BEAS-2B cells. Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. Indeed, purified inflammatory cytokines such as TNF-alpha and IL-6 up-regulated Tn levels in gingival fibroblasts. Furthermore, TNF-alpha was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. Since Cosmc, a chaperone for T-synthase, is known to negatively regulate Tn levels, our results suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis.
引用
收藏
页码:61930 / 61944
页数:15
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