Decreased Expression of LAMB3 Is Associated with Esophageal Cancer Stem Cell Formation.

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.