Abstract
BackgroundRecent studies have reported essential roles for various intracellular pH regulators in epithelial carcinogenesis and tumor progression. The aims of the present study were to investigate the role of anion exchanger 2 (AE2) in the regulation of tumor progression-related genes and the prognostic value of its expression in esophageal squamous cell carcinoma (ESCC).ResultsAE2 was strongly expressed in KYSE170 and TE13 cells. The depletion of AE2 in these cells increased cell migration and inhibited the induction of apoptosis. The results of the microarray analysis revealed that various matrix metalloproteinase (MMP) signaling pathway-related genes, such as MMP1, MMP12, and TIMP4, were up- or down-regulated in AE2-depleted KYSE170 cells. Immunohistochemical staining showed that AE2 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its expression pattern at the invasive front of the tumor was related to the pT category. Prognostic analyses revealed that the low-grade expression of AE2 at the invasive front was associated with shorter postoperative survival.ConclusionsThe results of the present study suggest that reductions in AE2 in ESCC enhance cellular movement by activating MMP signaling pathways and are related to a poor prognosis in patients with ESCC.MethodsIn human ESCC cell lines, knockdown experiments were conducted using AE2 siRNA, and the effects on cellular movement and survival were analyzed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy.
Highlights
Recent studies indicated that cytoplasmic pH regulated by ion transporters plays essential roles in various fundamental mechanism of tumor cells [1,2,3,4]
The results of the present study suggest that reductions in anion exchanger 2 (AE2) in esophageal squamous cell carcinoma (ESCC) enhance cellular movement by activating matrix metalloproteinase (MMP) signaling pathways and are related to a poor prognosis in patients with ESCC
In order to clarify the role of AE2 in ESCC, we examined 5 ESCC cell lines: TE2, TE5, TE9, TE13, and
Summary
Recent studies indicated that cytoplasmic pH regulated by ion transporters plays essential roles in various fundamental mechanism of tumor cells [1,2,3,4]. We previously investigated the functions of ion transporters [8, 9], water channels [10], and pHi regulators including AE1 [11], NHE1 [12], and CA12 [13] in esophageal squamous cell carcinoma (ESCC). Recent studies have reported essential roles for various intracellular pH regulators in epithelial carcinogenesis and tumor progression. The aims of the present study were to investigate the role of anion exchanger 2 (AE2) in the regulation of tumor progression-related genes and the prognostic value of its expression in esophageal squamous cell carcinoma (ESCC)
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