Small peritoneal macrophages are accelerators of peritoneal metastasis of colorectal cancer.

Abstract

Background: The peritoneal cavity (PerC) constitutes a distinct anatomical compartment that harbors various subpopulations of peritoneal macrophages. However, there remains a significant gap in our understanding of the functions of these macrophage subpopulations in the context of peritoneal metastasis of colorectal cancer (PM-CRC) and their roles in the tumor progression process. This investigation seeks to analyze the characteristics of large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs), in the context of PM-CRC.

Methods: A murine model of PM-CRC was developed through the intraperitoneal administration of the MC38 colorectal cancer cell line into C57BL/6 mice. Peritoneal effusions were subsequently collected at various time points post-injection and subjected to analysis via flow cytometry, cell co-culture assays, among other techniques. Additionally, clodronate liposomes were employed to deplete peritoneal macrophages in order to investigate the impact of SPMs on tumor progression and survival in the PM-CRC mouse model.

Results: The findings of this study demonstrated a significant increase in the number of SPMs during the progression of PM-CRC, concomitant with a decrease in the proportion of LPMs. Notably, SPMs exhibited a macrophage phenotype conducive to tumor growth. In the PM-CRC mouse model, the dynamic escalation of SPMs following lipopolysaccharide stimulation was associated with a reduced survival rate. However, the depletion of SPMs using clodronate liposomes in the later stages of the model effectively extended the survival period in cases of PM-CRC.

Conclusions: The findings of this study suggest that SPMs acts as a catalyst in the progression of peritoneal metastasis in colorectal cancer, thereby identifying it as a potential therapeutic target for managing this condition.