Xi X, Deng T, DU B
Department of Immunology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Oct 20;44(10):1866-1873. doi: 10.12122/j.issn.1673-4254.2024.10.04.
To investigate the effect of human colorectal fibroblast (CCD-18Co)-conditioned medium (CCD18-Co-CM) on biological behaviors of colorectal cancer (CRC) cells and explore the possible molecular mechanisms.
Real-time cellular analysis (RTCA), clone formation assay and wound healing assay were used to analyze the changes in proliferation, clone formation, and migration abilities of CRC cell lines HCT116 and Caco-2 treated with CCD18-Co-CM. Western blotting was used to detect the changes in ATK, ERK and STAT3 signaling pathways in the CRC cells activated by CCD18-Co-CM. The effect of CCD18-Co-CM on spheroidization ability of the cells was assessed with sphere-formation assay, and the changes in expressions of CRC stemness markers were detected using RT-PCR.
CCD-18Co-CM significantly promoted proliferation, colony formation, and migration of HCT116 and Caco-2 cells, enhanced sphere-forming ability and expressions of CRC stemness markers, and increased ERK phosphorylation in the cells. Treatment with SCH772984 effectively inhibited CCD-18Co-CM-induced ERK signaling pathway activation, suppressed the malignant phenotype, and lowered the sphere-forming ability and expression of stemness markers of the two CRC cells.
Colorectal fibroblasts promote malignant phenotype of CRC cells by activating the ERK signaling pathway.
探讨人结肠成纤维细胞（CCD - 18Co）条件培养基（CCD18 - Co - CM）对结肠癌细胞生物学行为的影响，并探索其可能的分子机制。
采用实时细胞分析（RTCA）、克隆形成实验和伤口愈合实验分析经CCD18 - Co - CM处理的结肠癌细胞系HCT116和Caco - 2的增殖、克隆形成及迁移能力的变化。采用蛋白质免疫印迹法检测经CCD18 - Co - CM激活的结肠癌细胞中ATK、ERK和STAT3信号通路的变化。用成球实验评估CCD18 - Co - CM对细胞成球能力的影响，并用逆转录聚合酶链反应（RT - PCR）检测结肠癌细胞干性标志物表达的变化。
CCD - 18Co - CM显著促进HCT116和Caco - 2细胞的增殖、集落形成和迁移，增强细胞的成球能力及结肠癌细胞干性标志物的表达，并增加细胞中ERK磷酸化水平。用SCH772984处理可有效抑制CCD - 18Co - CM诱导的ERK信号通路激活，抑制两种结肠癌细胞的恶性表型，降低其成球能力及干性标志物的表达。
结肠成纤维细胞通过激活ERK信号通路促进结肠癌细胞的恶性表型。
