The Role of Tumor-associated Macrophages in Colorectal Peritoneal Metastasis in Mice.

Introduction: In the tumor microenvironment, macrophages function as M1 macrophages, which cause cytotoxicity to tumor cells in the early stages, and M2 macrophages, which contribute to the proliferation of cancer cells in the late stages. This study aimed to examine the mechanism of action of macrophages in ascites using a peritoneal dissemination mouse model of colorectal cancer.

Materials and methods: Mouse models of peritoneal dissemination were created by injecting murine colorectal cancer cells into the abdominal cavity of non-obese diabetic/severely combined immunodeficient mice. Surface markers for M1 (CD38, CD68) and M2 (CD83, CD206) were used for macrophage differentiation via flow cytometry. Quantitative PCR and microarray gene expression analyses were performed on macrophages isolated from ascites. Additionally, a macrophage inhibitor (clodronate) and IL-10 inhibitor (AS101) were injected intra-abdominally, and the weight of peritoneally disseminated nodules was compared.

Results: M1 macrophage counts showed no change over time, while M2 counts and the expression of arginase 1 and IL-10 increased. Clodronate administration significantly reduced the weight of peritoneally disseminated nodules. and AS101 administration reduced tumor size.

Conclusion: Our findings indicate that cytokine and gene expression analyses of TAMs should be further explored to improve targeted anticancer therapy.