Yang Wanli, Jiang Feng, Xu Lixia, Pang Nan, Yang Chao, Yu Ruihua, Chen Haiqun
Translational Institute for Cancer Pain, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, China.
Department of General Surgery, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, China.
Transl Cancer Res. 2025 Mar 30;14(3):1626-1637. doi: 10.21037/tcr-24-1707. Epub 2025 Mar 14.
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.
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.
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.
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.
腹膜腔（PerC）构成一个独特的解剖区域，其中含有各种亚群的腹膜巨噬细胞。然而，在结直肠癌腹膜转移（PM-CRC）的背景下，我们对这些巨噬细胞亚群的功能及其在肿瘤进展过程中的作用的理解仍存在重大差距。本研究旨在分析PM-CRC背景下大腹膜巨噬细胞（LPMs）和小腹膜巨噬细胞（SPMs）的特征。
通过向C57BL/6小鼠腹腔内注射MC38结肠癌细胞系建立PM-CRC小鼠模型。随后在注射后的不同时间点收集腹腔积液，并通过流式细胞术、细胞共培养试验等技术进行分析。此外，使用氯膦酸脂质体清除腹膜巨噬细胞，以研究SPMs对PM-CRC小鼠模型中肿瘤进展和生存的影响。
本研究结果表明，在PM-CRC进展过程中，SPMs数量显著增加，同时LPMs比例下降。值得注意的是，SPMs表现出有利于肿瘤生长的巨噬细胞表型。在PM-CRC小鼠模型中，脂多糖刺激后SPMs的动态增加与生存率降低相关。然而，在模型后期使用氯膦酸脂质体清除SPMs有效地延长了PM-CRC病例的生存期。
本研究结果表明，SPMs在结直肠癌腹膜转移进展中起催化作用，从而将其确定为治疗这种疾病的潜在靶点。
