The expression and functional analysis of the sialyl-T antigen in prostate cancer

Abstract

Aberrant glycosylation is a featured characteristic of cancer and plays a role in cancer pathology; thus an understanding of the compositions and functions of glycans is critical for discovering diagnostic biomarkers and therapeutic targets for cancer. In this study, we used MALDI-TOF-MS analysis to determine the O-glycan profiles of prostate cancer cells metastasized to bone (PC-3), brain (DU145), lymph node (LNCaP), and vertebra (VCaP) in comparison to immortalized RWPE-1 cells derived from normal prostatic tissue. Prostate cancer (CaP) cells exhibited an elevation of simple/short O-glycans, with a reduction of complex O-glycans, increased O-glycan sialylation and decreased fucosylation. Core 1 sialylation was increased dramatically in all CaP cells, and especially in PC-3 cells. The expression of Neu5Acα2-3Galβ1-3GalNAc- (sialyl-3T antigen) which is the product of α2,3-sialyltransferase-I (ST3Gal-I) was substantially increased. We therefore focused on exploring the possible function of ST3Gal-I in PC-3 cells. ST3Gal-I silencing studies showed that ST3Gal-I was associated with PC-3 cell proliferation, migration and apoptosis. Further in vivo studies demonstrated that down regulation of ST3Gal-I reduced the tumor size in xenograft mouse model, indicating that sialyl-3T can serve as a biomarker for metastatic prostate cancer prognosis, and that ST3Gal-I could be a target for therapeutic intervention in cancer treatment.

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Abbreviations

DR:

death receptor

MALDI-TOF-MS:

matrix assisted laser desorption ionization-time of flight mass spectrometry

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PBS:

phosphate buffered saline

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Funding

This work was supported by the National Natural Science Foundation of China [31700713]; Department of Science and Technology of Jilin Province [grant number 20200801066GH]; Jilin Province Development and Reform Commission [2019C049-9] to Y.G. and Prostate Cancer Fight Foundation, Canada to I.B.

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Correspondence to Yin Gao.

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The authors declare that they have no conflicts of interest.

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Prior to the experiments, the entire animal protocol was reviewed and approved by the Institution Animal Ethics Committee(Reference No. SY201905023), and adhered to the Guidelines on Humane Treatment to Lab Animals (2009).

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Ruifeng Bai and Xue Luan contributed equally to this work

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Bai, R., Luan, X., Zhang, Y. et al. The expression and functional analysis of the sialyl-T antigen in prostate cancer. Glycoconj J 37, 423–433 (2020). https://doi.org/10.1007/s10719-020-09927-x

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Keywords

  • Prostate cancer
  • Glycosylation
  • Mass spectrometry
  • α2,3-sialyltransferase
  • Sialyl-3T antigen