The cytokine-cosmc signaling axis upregulates the tumorassociated carbohydrate antigen Tn

Chia Wen Ho, Chi Yu Lin, Yi Wei Liaw, Hsiao Ling Chiang, Yu Tang Chin, Rui Lan Huang, Hung Cheng Lai, Yaw Wen Hsu, Po Jan Kuo, Chiao En Chen, Hung Yun Lin, Jacqueline Whang-Peng, Shin Nieh, Earl Fu, Leroy F. Liu, Jaulang Hwang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Tn antigen (GalNAc-β-O-Ser/Thr), a mucin-type O-linked glycan, is a wellestablished 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 HrasG12V-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-β and IL-6 up-regulated Tn levels in gingival fibroblasts. Furthermore, TNF-β 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.

Original languageEnglish
Pages (from-to)61930-61944
Number of pages15
JournalOncotarget
Volume7
Issue number38
DOIs
Publication statusPublished - 2016

Fingerprint

Up-Regulation
Carbohydrates
Cytokines
Conditioned Culture Medium
Inflammation
Neoplasms
Fibroblasts
CpG Islands
Mucins
Tumor Biomarkers
Genes
Polysaccharides
Monocytes
Interleukin-6
Down-Regulation
Messenger RNA
Tn antigen
Proteins

Keywords

  • Cosmc
  • Cytokines
  • Hypermethylation
  • Tn antigen
  • Tumor-associated carbohydrate

ASJC Scopus subject areas

  • Oncology

Cite this

Ho, C. W., Lin, C. Y., Liaw, Y. W., Chiang, H. L., Chin, Y. T., Huang, R. L., ... Hwang, J. (2016). The cytokine-cosmc signaling axis upregulates the tumorassociated carbohydrate antigen Tn. Oncotarget, 7(38), 61930-61944. https://doi.org/10.18632/oncotarget.11324

The cytokine-cosmc signaling axis upregulates the tumorassociated carbohydrate antigen Tn. / Ho, Chia Wen; Lin, Chi Yu; Liaw, Yi Wei; Chiang, Hsiao Ling; Chin, Yu Tang; Huang, Rui Lan; Lai, Hung Cheng; Hsu, Yaw Wen; Kuo, Po Jan; Chen, Chiao En; Lin, Hung Yun; Whang-Peng, Jacqueline; Nieh, Shin; Fu, Earl; Liu, Leroy F.; Hwang, Jaulang.

In: Oncotarget, Vol. 7, No. 38, 2016, p. 61930-61944.

Research output: Contribution to journalArticle

Ho, CW, Lin, CY, Liaw, YW, Chiang, HL, Chin, YT, Huang, RL, Lai, HC, Hsu, YW, Kuo, PJ, Chen, CE, Lin, HY, Whang-Peng, J, Nieh, S, Fu, E, Liu, LF & Hwang, J 2016, 'The cytokine-cosmc signaling axis upregulates the tumorassociated carbohydrate antigen Tn', Oncotarget, vol. 7, no. 38, pp. 61930-61944. https://doi.org/10.18632/oncotarget.11324
Ho, Chia Wen ; Lin, Chi Yu ; Liaw, Yi Wei ; Chiang, Hsiao Ling ; Chin, Yu Tang ; Huang, Rui Lan ; Lai, Hung Cheng ; Hsu, Yaw Wen ; Kuo, Po Jan ; Chen, Chiao En ; Lin, Hung Yun ; Whang-Peng, Jacqueline ; Nieh, Shin ; Fu, Earl ; Liu, Leroy F. ; Hwang, Jaulang. / The cytokine-cosmc signaling axis upregulates the tumorassociated carbohydrate antigen Tn. In: Oncotarget. 2016 ; Vol. 7, No. 38. pp. 61930-61944.
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AU - Chin, Yu Tang

AU - Huang, Rui Lan

AU - Lai, Hung Cheng

AU - Hsu, Yaw Wen

AU - Kuo, Po Jan

AU - Chen, Chiao En

AU - Lin, Hung Yun

AU - Whang-Peng, Jacqueline

AU - Nieh, Shin

AU - Fu, Earl

AU - Liu, Leroy F.

AU - Hwang, Jaulang

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