Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression

  • Guo, Jie (Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology) ;
  • Liao, Mengfan (Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology) ;
  • Hu, Xianmin (Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology) ;
  • Wang, Jun (Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology)
  • Received : 2021.05.27
  • Accepted : 2021.07.22
  • Published : 2021.09.30
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Abstract

As a pancreatic inflammatory marker, regenerating islet-derived protein 3A (Reg3A) plays a key role in inflammation-associated pancreatic carcinogenesis by promoting cell proliferation, inhibiting apoptosis, and regulating cancer cell migration and invasion. This study aimed to reveal a novel immuno-regulatory mechanism by which Reg3A modulates tumour-promoting responses during pancreatic cancer (PC) progression. In an in vitro Transwell system that allowed the direct co-culture of human peripheral blood-derived dendritic cells (DCs) and Reg3A-overexpressing/ silenced human PC cells, PC cell-derived Reg3A was found to downregulate CD80, CD83 and CD86 expression on educated DCs, increase DC endocytic function, inhibit DC-induced T lymphocyte proliferation, reduce IL-12p70 production, and enhance IL-23 production by DCs. The positive effect of tumour-derived Reg3A-educated human DCs on PC progression was demonstrated in vivo by intraperitoneally transferring them into PC-implanted severe combined immunodeficiency (SCID) mice reconstituted with human T cells. A Reg3A-JAK2/STAT3 positive feedback loop was identified in DCs educated with Reg3A. In conclusion, as a tumour-derived factor, Reg3A acted to block the differentiation and maturation of the most important antigen-presenting cells, DCs, causing them to limit their potential anti-tumour responses, thus facilitating PC escape and progression.

Keywords

Acknowledgement

This work was funded by grants from the National Natural Science Foundation of China (81602108, 71974153) and the Provincial College Students' Innovative Entrepreneurial Training Program in Hubei (201810488115).

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