Lan Guanghui, Lin Zongwei, Zhang Jinhui, Liu Li, Zhang Jianjun, Zheng Lei, Luo Qiong
Shenzhen Hospital, Southern Medical University, Shenzhen 518101, People's Republic of China.
GI Surgery, The People's Hospital of Nanshan District, Shenzhen, 518067, People's Republic of China.
Onco Targets Ther. 2019 Apr 16;12:2869-2878. doi: 10.2147/OTT.S199046. eCollection 2019.
Recently, embryonic microenvironment is being known for its non-permissive property for tumor growth. However, the regulatory mechanism to maintain the balance between differentiation and tumorigenicity of cancer cell in microenvironment is not well understood. qRT-PCR was performed to detect the levels of gene expression in HT29, LoVo and Caco-2 colorectal cancer cells, and Western blot was used to measure the protein levels. Cell migration and apoptosis were measured by Transwell and flow cytometry assays. Cancer cell markers were detected using immunohistochemical staining. In vivo tumor formation assay was conducted by subcutaneous injection of embryonic microenvironment-treated cancer cells. Colorectal cancer cell lines were treated with human embryonic stem cell conditioned culture and then collected for in vivo tumor formation assay and in vitro assays assessing the aggressive properties. We found exposure of cancer cells in human ES cultures resulted in inhibition of growth, migration of tumor cells. Moreover, we found that manipulation of Notch pathway in the ES cells microenvironment could influence the stemness of tumor. We specifically discovered that some factor in the embryonic microenvironment could suppress Notch1 pathway in the cancer cells, leading to a reduction in tumorigenesis and invasiveness. This study may provide another evidence to understand the crosstalk between tumor cells and embryonic environment and may offer new therapeutic strategies to inhibit colorectal cancer progression.
最近，胚胎微环境因其对肿瘤生长的非许可特性而为人所知。然而，在微环境中维持癌细胞分化与致瘤性之间平衡的调控机制尚未完全清楚。采用qRT-PCR检测HT29、LoVo和Caco-2结肠癌细胞中的基因表达水平，并用蛋白质印迹法测定蛋白质水平。通过Transwell和流式细胞术检测细胞迁移和凋亡。使用免疫组织化学染色检测癌细胞标志物。通过皮下注射经胚胎微环境处理的癌细胞进行体内肿瘤形成试验。用人类胚胎干细胞条件培养基处理结肠癌细胞系，然后收集用于体内肿瘤形成试验和评估侵袭性的体外试验。我们发现癌细胞暴露于人类胚胎干细胞培养物中会导致肿瘤细胞生长和迁移受到抑制。此外，我们发现对胚胎干细胞微环境中的Notch信号通路进行调控可影响肿瘤的干性。我们特别发现胚胎微环境中的某些因子可抑制癌细胞中的Notch1信号通路，从而导致肿瘤发生和侵袭性降低。本研究可能为理解肿瘤细胞与胚胎环境之间的相互作用提供另一证据，并可能为抑制结肠癌进展提供新的治疗策略。
