Dynamic changes and functions of macrophages and M1/M2 subpopulations during ulcerative colitis-associated carcinogenesis in an AOM/DSS mouse model

The high risk of developing colorectal carcinoma (CRC), from ulcerative colitis (UC), is well known. Macrophages are widely distributed immune cells that have an indispensable role in UC, as well as in CRC. However, little is currently known about the dynamic changes that occur in macrophage and M1/M2 macrophage subpopulations, during UC-associated carcinogenesis. The aim of the present study was to investigate the alteration of colorectal macrophages and M1/M2 macrophage subpopulations during UC-associated carcinogenesis. Both expression level alterations and functional changes were determined during UC-associated carcinogenesis in an azoxymethane/dextran sodium sulfate-induced chemically colitis-associated carcinoma mouse model of Crj:CD-1 (ICR) mice. Notable evidence from immunohistochemistry, flow cytometry, cytokine detection, and gene expression analyses demonstrated that M2 macrophages have a critical role in CRC initiation, promotion, and metastasis. M2 macrophages are associated with unbalanced pro-inflammatory and anti-inflammatory axes and aberrant enhancement of migration/invasion-associated factors. Functional changes, similar to M2 polarized macrophages, were shown to occur in the M1 macrophages, without phenotypical changes, during the development of carcinoma and metastasis. The results of the present study suggest that M2 macrophages have a pro-tumor role during UC-associated carcinogenesis. Furthermore, similar functional changes occurred in the M1 macrophages, without polarization alterations, during carcinogenesis and metastasis.