School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Gaozhou Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine, Gaozhou, China.
Cancer Med. 2024 Sep;13(18):e70245. doi: 10.1002/cam4.70245.
Colorectal cancer (CRC) is a malignancy that arises within the gastrointestinal tract. Despite ongoing research, the etiology and pathogenesis of CRC remain elusive; particularly, the distribution and characteristics of tumor-associated macrophages is currently an active area of investigation in understanding the pathological progression and prevention of CRC.
This study utilized CRC patient surgical samples, mouse models of colitis-associated cancer, colonic organoid, and co-culture cell line to examine the changes in CD11b/CD86 at different pathological region and detect the Wnt signaling pathway activity.
Our findings revealed a sensitive and increased expression of CD11b from the early to the advanced CRC tissues and correlated with poor prognosis, while CD86 expression was reduced in advanced CRC tissues. CD133 expression was also elevated in advanced CRC tissues and mainly co-localized with CD11b, suggesting a positive regulatory effect of CD11b and CD133 expression that may contribute to CRC progression. In AOM/DSS mouse models, activation of the Wnt signaling pathway was associated with increased CD133 and CD11b expression. In vitro, THP-1 cell was induced to high expression of CD11b, and the above conditional cultural medium enhanced HCT116 cell colony number and CD133 protein expression. Furthermore, colonic crypts from AOM/DSS mouse models were isolated to culture, and the colonic organoids exhibited dilation and significant increases expression of CD133 and β-Catenin/N-P-B-Catenin.
CD11b might be an important factor to participate the progress of CRC. And the high CD11b of CRC microenviroment might potentially promote CD133 expression and associate with Wnt signal activation.
结直肠癌（CRC）是一种起源于胃肠道的恶性肿瘤。尽管在不断研究，但 CRC 的病因和发病机制仍然难以捉摸；特别是肿瘤相关巨噬细胞的分布和特征，目前是研究理解 CRC 病理进展和预防的一个活跃领域。
本研究利用 CRC 患者手术样本、结肠炎相关癌症小鼠模型、结直肠类器官和共培养细胞系，研究不同病理区域 CD11b/CD86 的变化，并检测 Wnt 信号通路的活性。
我们的研究结果显示，从早期到晚期 CRC 组织中 CD11b 的表达敏感且增加，并与预后不良相关，而 CD86 的表达在晚期 CRC 组织中降低。CD133 在晚期 CRC 组织中也呈高表达，且主要与 CD11b 共定位，提示 CD11b 和 CD133 表达的正调节作用可能有助于 CRC 的进展。在 AOM/DSS 小鼠模型中，Wnt 信号通路的激活与 CD133 和 CD11b 表达的增加有关。在体外，THP-1 细胞被诱导高表达 CD11b，上述条件性培养上清液增强了 HCT116 细胞集落数量和 CD133 蛋白表达。此外，从 AOM/DSS 小鼠模型中分离结肠隐窝进行培养，结肠类器官表现出扩张，CD133 和 β-连环蛋白/N-P-B-连环蛋白的表达显著增加。
CD11b 可能是 CRC 进展的重要因素。CRC 微环境中高 CD11b 可能潜在地促进 CD133 表达，并与 Wnt 信号激活相关。
