Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis

  • Authors:
    • Qiang Yan
    • Wen-Bin Yuan
    • Xu Sun
    • Ming-Jie Zhang
    • Feng Cen
    • Shi-Yu Zhou
    • Wan-Bo Wu
    • Yong‑Can Xu
    • Li-Hui Tong
    • Zhi-Hong Ma
  • View Affiliations

  • Published online on: March 15, 2018     https://doi.org/10.3892/ijo.2018.4318
  • Pages: 1651-1660
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Abstract

Pancreatic cancer is one of the most lethal types of cancer; owing to low early detection rates and high metastasis rates, it is associated with an extremely poor prognosis. Therefore, a better understanding of the molecular mechanisms that underlie its metastasis and the identification of potential prognostic biomarkers are urgently required. Although high expression levels of asparaginyl endopeptidase (AEP) have been detected in various types of solid tumor, the expression and functions of AEP in pancreatic carcinomas have yet to be determined. The present study aimed to examine the putative functions of AEP in pancreatic carcinoma. Immunohistochemical analysis revealed that AEP was highly expressed in pancreatic cancer tissues compared with adjacent normal tissues. Patients with high AEP expression exhibited a significantly shorter overall survival time. Results from multivariate Cox regression analysis revealed that AEP was an independent prognostic factor for overall survival. Gain- and loss-of-function experiments demonstrated that knockdown of AEP expression significantly reduced the invasive ability of pancreatic cancer cells, whereas overexpression of AEP increased the invasive ability. In addition, AEP was detected in exosomes that were derived from cultured pancreatic ductal adenocarcinoma cells (PDACs) and in the serum from patients with PDAC. The Matrigel-Transwell invasion assay revealed that exosomes enriched with AEP were able to enhance the invasive ability of PDAC cells, whereas exosomes lacking AEP decreased the invasive ability. Furthermore, results from the present study suggested that AEP may be crucial for activation of the phosphoinositide 3-kinase/RAC‑α serine/threonine-protein kinase signaling pathway in PDAC cells. The present study data indicated that high AEP expression may be important for pancreatic carcinoma progression in an exosome-dependent manner, and that AEP may be an independent indicator of poor prognosis in patients with PDAC and may be a novel prognostic biomarker or therapeutic target in pancreatic carcinoma.
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May-2018
Volume 52 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yan Q, Yuan W, Sun X, Zhang M, Cen F, Zhou S, Wu W, Xu YC, Tong L, Ma Z, Ma Z, et al: Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis. Int J Oncol 52: 1651-1660, 2018
APA
Yan, Q., Yuan, W., Sun, X., Zhang, M., Cen, F., Zhou, S. ... Ma, Z. (2018). Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis. International Journal of Oncology, 52, 1651-1660. https://doi.org/10.3892/ijo.2018.4318
MLA
Yan, Q., Yuan, W., Sun, X., Zhang, M., Cen, F., Zhou, S., Wu, W., Xu, Y., Tong, L., Ma, Z."Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis". International Journal of Oncology 52.5 (2018): 1651-1660.
Chicago
Yan, Q., Yuan, W., Sun, X., Zhang, M., Cen, F., Zhou, S., Wu, W., Xu, Y., Tong, L., Ma, Z."Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis". International Journal of Oncology 52, no. 5 (2018): 1651-1660. https://doi.org/10.3892/ijo.2018.4318