Biglycan regulated colorectal cancer progress by modulating enteric neuron-derived IL-10 and abundance of Bacteroides thetaiotaomicron

  • iScience. 2023 Aug 2;26(9):107515. doi: 10.1016/j.isci.2023.107515.
Yuyu Xu  1 ,  Fei Wang  1  2 ,  Kai Mi  1 ,  Xinyuan Wang  1 ,  Danlei Wang  1 ,  Qing Zhao  1 ,  Jingjing Wang  1 ,  Zhi Liu  1 ,  Qingqing Zhang  1 ,  Yang Liu  1 ,  Xuemei Zhang  1 ,  Xingyin Liu  1  3
Affiliations
  • 1. Department of Pathogen Biology-Microbiology Division, State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Pathogen of Jiangsu Province, Key Laboratory of Human Functional Genomics of Jiangsu Province, Center of Global Health, Nanjing Medical University, Nanjing 211166, China.
  • 2. The Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu 214151, China.
  • 3. The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China.
PMID: 37664615 DOI: 10.1016/j.isci.2023.107515
Abstract

Biglycan (BGN) is a proteoglycan with branch chains and highly expressed in enteric neurons in the tumor tissue of colorectal Cancer (CRC), which is negatively associated with survival rates in patients with CRC. However, how the proteoglycan promotes the progress of CRC through interacting with bacteria and regulating the immune response of enteric neurons remains largely unknown. In the present study, we found that biglycan deficiency changed tumor distribution in a colitis-associated colon Cancer model. Furthermore, we revealed that BGN deficiency inhibits tumor growth in an allograft tumor model and the migration of Cancer cell by upregulating interleukin-10 expression in enteric neurons. Significantly, we demonstrated that biglycan deficiency enriched the abundance of Bacteroides thetaiotaomicron through competing with it for chondroitin sulfate to inhibit CRC progress. Our work provided new insights into the interaction between host proteoglycan and gut microbiota as well as the role of enteric neurons in the tumor microenvironment.

Keywords
Cancer; Health sciences; Microbiome.
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