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Journal of Cancer Prevention

Original Article

J Cancer Prev 2022; 27(1): 31-41

Published online March 30, 2022

https://doi.org/10.15430/JCP.2022.27.1.31

© Korean Society of Cancer Prevention

Mannose Attenuates Colitis-Associated Colorectal Tumorigenesis by Targeting Tumor-Associated Macrophages

Qinglong Liu1,2 , Xiaojing Li1,2 , Hao Zhang1,2,3 , Haitao Li1,2

1State Key Laboratory of Food Science and Technology, Jiangnan University, 2School of Food Science and Technology, Jiangnan University, 3National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu, China

Correspondence to :
Haitao Li, E-mail: liht@jiangnan.edu.cn, https://orcid.org/0000-0002-1493-8679

Received: February 5, 2022; Revised: March 3, 2022; Accepted: March 7, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mannose has recently drawn extensive attention for its substantial anti-cancer activities, but the underlying mechanism remains largely unclear. The aim of this study was to investigate the effects of mannose on experimental colitis-associated colorectal tumorigenesis and underlying mechanisms. Data clearly showed that at plasma concentrations achieved after oral administration, mannose slightly affected malignancy of tumor cells or tumor promoter-induced transformation of pre-neoplastic cells, but substantially suppressed manifestation of the M2-like phenotype of tumor-associated macrophages (TAMs) in a cancer cell and macrophage co-culture model. Mechanistically, mannose might greatly impair the production of tumor cell-derived lactate which has a critical role in the functional polarization of TAMs. Importantly, oral administration of mannose protected mice against colitis-associated colorectal tumorigenesis by normalizing TAM polarization. Collectively, these findings highlight the importance of TAMs in colorectal tumorigenesis, and provide a rationale for introducing mannose supplementation to patients suffering from inflammatory bowel diseases.

Keywords: Colorectal cancer, Mannose, Tumor-associated macrophages, Lactate

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