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

Yuyu Xu; Fei Wang; Kai Mi; Xinyuan Wang; Danlei Wang; Qing Zhao; Jingjing Wang; Zhi Liu; Qingqing Zhang; Yang Liu; Xuemei Zhang; Xingyin Liu

doi:10.1016/j.isci.2023.107515

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. eCollection 2023 Sep 15.

Authors

Yuyu Xu¹, Fei Wang^{1

2}, Kai Mi¹, Xinyuan Wang¹, Danlei Wang¹, Qing Zhao¹, Jingjing Wang¹, Zhi Liu¹, Qingqing Zhang¹, Yang Liu¹, Xuemei Zhang¹, 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.

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.