DPP3 expression promotes cell proliferation and migration in vitro and tumor growth in vivo that associates with poor prognosis of esophageal carcinoma

Abstract

Background Dipeptidyl peptidase III (DPP3) is a zinc-dependent metallopeptidase and elevated in a variety of malignant tumors, but the underlying mechanism is not well understood so far. Here we investigated the association of esophageal carcinogenesis with the regulation of DPP3 expression by tissue-based quantitative analysis and the depletion of DPP3 expression in esophageal cancer cells and xenograft model. Methods The expression level of DPP3 in esophageal cancer tissues and adjacent normal tissues was detected in 93 cases of tissue biopsies collected from patients diagnosed with esophageal carcinoma by immunohistochemistry. The effect of DPP3 expression on cell proliferation, migration or apoptosis was determined in DPP3-depleted esophageal cancer cells created by infection with the lentivirus containing the shRNA specific to human DPP3 mRNA sequence followed by detection at the cellular level using celigo cell count assay, flow cytometry, wound-healing assay and trans-well assay as well as chip screening with a Human Apoptosis Antibody Array kit, which enables the quantitative detection of 43 apoptosis-related genes. A xenograft model was applied to the detection of tumor growth and invasion of DPP3-depleted cancer cells in nude mice. Results DPP3 expression was elevated in esophageal cancer tissues compared with adjacent non-tumor tissues (normal controls) with statistical significance (P < 0.05), and associated with poor prognosis of esophageal carcinoma. The DPP3-depletion resulted in a reduced cell proliferation and migration and enhanced cell-cycle arrest and apoptosis of esophageal cancer cells, and lead to the inhibition of tumor growth and invasion in xenograft model. In addition, DPP3-depletion was associated with the upregulation of pro-apoptotic proteins and the downregulation of anti-apoptotic proteins. Conclusions These findings suggest that DPP3 may promote cell proliferation, migration and survival of esophageal cancer cells in vitro, and tumor growth and invasion of esophageal carcinoma in vivo and this might serve as a molecular target for tumor therapy.