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Abstract：
Purpose: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer. The main cause of death in ESCC is related to relapse, metastasis, and resistance to cancer therapy. Recent studies have shown that a minor subset of cancer cells, known as cancer stem cells (CSCs), are responsible for tumor formation initiation and cancer progression. Understanding the genes associated with CSCs and metastasis can help in targeted cancer therapy. The aim of this study was to assess the expression of LAMB3 and TOP2A metastasis-associated genes in CSCs and adherent cells in the xenograft mouse model. Methods: Esophageal CSCs were enriched by the sphere formation method. The expression level of LAMB3 and TOP2A genes were evaluated in spheres and adherent cells in vitro by qRT-PCR. A xenograft mouse model was established to investigate the tumorigenesis and metastasis potential by subcutaneous and tail vein injection of CSCs and adherent YM-1 cells. Consequently, LAMB3 and TOP2A expression at the mRNA level was assessed in tumors. Immunohistochemistry was also used to evaluate the LAMB3 expression at the protein level in tumors. Results: CSCs-derived tumor was developed more quickly than the adherent cells-derived tumor. LAMB3 at mRNA and protein level was significantly down-regulated in sphere-derived tumor compared with adherent cells-derived tumor (P value <0.05). TOP2A expression was almost similar in both sphere cells and adherent cells and there was no significant difference. Conclusion: we concluded that YM-1 spheres have CSCs characteristics in vitro with high capability of tumorigenicity in vivo. Our results were also shown that the LAMB3 expression was decreased in YM-1 spheres suggesting LAMB3 association with sphere formation.
摘要：
目的：食管鳞状细胞癌（ESCC）是一种高度侵袭性的癌症。ESCC的主要死亡原因与复发有关，转移,和对癌症治疗的抵抗力。最近的研究表明，一小部分癌细胞，被称为癌症干细胞（CSC），负责肿瘤形成的启动和癌症的进展。了解与CSCs和转移相关的基因可以帮助靶向癌症治疗。这项研究的目的是评估异种移植小鼠模型中CSC和粘附细胞中LAMB3和TOP2A转移相关基因的表达。方法:采用球体形成法富集食管CSCs。通过qRT-PCR在体外球和贴壁细胞中评估LAMB3和TOP2A基因的表达水平。通过皮下和尾静脉注射CSCs和粘附的YM-1细胞，建立异种移植小鼠模型以研究肿瘤发生和转移潜力。因此,在肿瘤中评估mRNA水平的LAMB3和TOP2A表达。免疫组织化学还用于评估肿瘤中蛋白质水平的LAMB3表达。结果：CSC来源的肿瘤比粘附细胞来源的肿瘤发展更快。与贴壁细胞来源的肿瘤相比，球体来源的肿瘤中LAMB3的mRNA和蛋白水平明显下调（P值<0.05）。在球形细胞和贴壁细胞中TOP2A的表达几乎相似，没有显着差异。结论：我们得出结论，YM-1球体在体外具有CSCs特征，在体内具有较高的致瘤性。我们的结果还表明，LAMB3在YM-1球体中的表达降低，表明LAMB3与球体形成有关。
