DPP3 expression promotes cell proliferation and migration in vitro and tumour growth in vivo, which is associated with poor prognosis of oesophageal carcinoma

Abstract

Dipeptidyl peptidase III (DPP3), a zinc-dependent metallopeptidase, is upregulated in a variety of malignancies. However, little is known about its roles in the pathogenesis of these malignancies. The present study was designed to investigate the roles of DPP3 in the pathogenesis and progression of oesophageal cancer (EC). The expression level of DPP3 in EC tissues and adjacent normal tissues was detected in 93 cases of tissue biopsies collected from patients diagnosed with oesophageal carcinoma by immunohistochemistry. The effect of DPP3 expression on cell proliferation, migration or apoptosis was determined in DPP3-depleted EC cells created by infection with lentivirus containing short hairpin RNA specific to the human DPP3 mRNA sequence, followed by detection at the cellular level using a Celigo cell count assay, flow cytometry, wound-healing assay and Transwell 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 detect the tumour growth and invasion of DPP3-depleted cancer cells in nude mice. The results revealed that DPP3 expression was elevated in EC tissues compared with adjacent non-tumour tissues, and high DPP3 expression was significantly associated with poor prognosis. DPP3 depletion resulted in reduced cell proliferation and migration and enhanced cell cycle arrest and apoptosis of EC cells and led to the inhibition of tumour growth and invasion in a xenograft model. In addition, DPP3 depletion was associated with the upregulation of the proapoptotic proteins SMAC and p53 and the downregulation of the antiapoptotic proteins clAP-2, IGFBP-2 and TRAILR-4. Finally, DPP3 may promote cell proliferation, migration and survival of EC cells in vitro and tumour growth and invasion of oesophageal carcinoma in vivo, and thus may serve as a molecular target for tumour therapy.

Involvement of DPP3 in modulating oncological features and oxidative stress response in esophageal squamous cell carcinoma

“…Likewise, DPP3 down-regulation led to a higher apoptotic rate in these cells. This agrees with a recent report demonstrating that DPP3 down-regulation is associated with an enhancement in the expression of proapoptotic proteins and alteration in cell cycle distribution in ESCC cells [ 32 ]. The reduced proliferation rate and higher apoptotic rate in DPP3 knockdown cells might also be responsible for the observed reduction in colony size of ESCC cells after DPP3 knockdown.…”

“…DPP family members have emerged as critical regulators of cellular physiology [ 19 ]. Several reports on DPP3 have suggested its aberrant activity in cancers of multiple origins, such as breast cancer [ 20 , 26 , 42 ], lung cancer [ 24 ], ovarian cancer [ 22 ], endometrial cancer [ 22 ], colon cancer [ 30 ], and EC [ 32 ]. Many of these studies observed higher expression or activity of this peptidase in tumor tissues compared with normal tissues, suggesting its overexpression is common in cancers.…”

“…In the present study, we assessed the potential role of DPP3 in EC. A recent study revealed that DPP3 protein levels are higher in ESCC tissues compared with adjacent normal tissues [ 32 ]. Similarly, we assessed the mRNA expression of DPP3 in ESCC patients, which also suggested higher expression of this peptidase in tumor tissues compared with normal esophageal epithelia.…”

Identification of SH2 Domain-Containing Protein 3C as a Novel, Putative Interactor of Dipeptidyl Peptidase 3

“…Based on the current knowledge of DPP3 and SH2D3C and our own findings, we propose that their interaction represents a link between NRF2–KEAP1 mediated oxidative stress response and the regulation of cell migration through the NSP–Cas network. Currently, there is no evidence that these signaling pathways are related; however, there are reports that DPP3 depletion by shRNA reduces the cell migration of colon cancer cell lines HCT-116 and RKO [ 18 ] and esophageal cancer cell lines Eca-109 and TE-1 [ 28 ], although the exact mechanism of DPP3 involvement in cell migration was not elucidated. In addition, both DPP3 and p130Cas (interactor of SH2D3C) have been linked to bone development through the regulation of osteoclasts.…”

FAM111B Acts as an Oncogene in Bladder Cancer

“…A human apoptosis antibody array (Abcam, USA, Cat. Ab134001) was used to detect the expression levels of 43 human apoptosis markers [24][25][26]. T24 cells transfected with lentivirus were washed with PBS and lysed using cell lysis buffer.…”