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

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.