Abstract
BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas of the gastrointestinal tract. We assessed the relevance of Slug in measuring the invasive potential of ESCC cells in vitro and in vivo in immunodeficient mice.MethodsWe utilized RNA interference to knockdown Slug gene expression, and effects on survival and invasive carcinoma were evaluated using a Boyden chamber transwell assay in vitro. We evaluated the effect of Slug siRNA-transfection and Slug cDNA-transfection on E-cadherin and Bcl-2 expression in ESCC cells. A pseudometastatic model of ESCC in immunodeficient mice was used to assess the effects of Slug siRNA transfection on tumor metastasis development.ResultsThe EC109 cell line was transfected with Slug-siRNA to knockdown Slug expression. The TE13 cell line was transfected with Slug-cDNA to increase Slug expression. EC109 and TE13 cell lines were tested for the expression of apoptosis-related genes bcl-2 and metastasis-related gene E-cadherin identified previously as Slug targets. Bcl-2 expression was increased and E-cadherin was decreased in Slug siRNA-transfected EC109 cells. Bcl-2 expression was increased and E-cadherin was decreased in Slug cDNA-transfected TE13 cells. Invasion of Slug siRNA-transfected EC109 cells was reduced and apoptosis was increased whereas invasion was greater in Slug cDNA-transfected cells. Animals injected with Slug siRNA-transfected EC109 cells exhihited fewer seeded nodes and demonstrated more apoptosis.ConclusionsSlug down-regulation promotes cell apoptosis and decreases invasion capability in vitro and in vivo. Slug inhibition may represent a novel strategy for treatment of metastatic ESCC.
Highlights
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas of the gastrointestinal tract
TE13 was obtained from the Japanese Cell Resource Center for Biomedical Research (Sdai, Japan);EC109 cell lines showed the highest level of Slug expression and TE13 cell lines showed less Slug expression [17]
Slug modulates invasion in ESCC cells in vitro Recent data indicate that Slug expression is relevant for melanoma metastasis [20]
Summary
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas of the gastrointestinal tract. Surgical resection, and (neo-) adjuvant therapy, the overall survival for esophageal squamous cell carcinoma (ESCC), one of the most aggressive carcinomas of the gastrointestinal tract, remains lower than that of other solid tumors due to distant metastasis [1]. Multiple studies focusing on the effects of various biological factors on the malignant potential of ESCC have been conducted [2,3,4]. One of those factors is E-cadherin as the loss of E-cadherin is an important step in the process of epithelial-to-mesenchymal transition (EMT) in cancer [5,6,7,8]. In ESCC, loss of E-cadherin expression is associated with tumor invasiveness, metastasis, and prognosis [2,9,10,11]
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