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Published on: March 10, 2015
Mannose Attenuates Colitis-Associated Colorectal Tumorigenesis by Targeting Tumor-Associated Macrophages
Qinglong Liu1,2, Xiaojing Li1,2, Hao Zhang1,2,3
1State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
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.
Insights
Mannose supplementation suppressed colorectal cancer in mice by normalizing tumor-associated macrophages (TAMs). This sugar impacts cancer development by reducing lactate production, offering a potential therapeutic strategy for inflammatory bowel diseases.
Area of Science:
- Oncology
- Immunology
- Metabolism
Background:
- Mannose exhibits anti-cancer properties, but its precise mechanisms are not fully understood.
- Colorectal tumorigenesis is influenced by the tumor microenvironment, particularly tumor-associated macrophages (TAMs).
Purpose of the Study:
- To investigate the impact of mannose on colitis-associated colorectal tumorigenesis.
- To elucidate the underlying mechanisms by which mannose affects cancer development.
Main Methods:
- Oral administration of mannose to mice with experimental colitis-associated colorectal tumorigenesis.
- Co-culture models of cancer cells and macrophages to assess TAM phenotype.
- Analysis of lactate production by tumor cells.
Main Results:
- Mannose administration significantly suppressed colorectal tumorigenesis in mice.
- Mannose normalized the M2-like phenotype of tumor-associated macrophages (TAMs).
- Mannose impaired tumor cell lactate production, a key factor in TAM polarization.
Conclusions:
- Mannose shows therapeutic potential for colitis-associated colorectal cancer by modulating TAM polarization.
- Targeting TAMs through mannose supplementation could be a viable strategy for inflammatory bowel disease patients.
- Lactate production by tumor cells plays a critical role in TAM-mediated tumorigenesis.
