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

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4 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

Keywords

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

ASJC Scopus subject areas

  • Oncology

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    Ho, C. W., Lin, C. Y., Liaw, Y. W., Chiang, H. L., Chin, Y. T., Huang, R. L., Lai, H. C., Hsu, Y. W., Kuo, P. J., Chen, C. E., Lin, H. Y., Whang-Peng, J., Nieh, S., Fu, E., Liu, L. F., & 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