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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

High Level of Adropin Promotes the Progression of Pancreatic Ductal Adenocarcinoma

Author(s): Jilong Hu, Qinrong Wu, Qunhua Ding, Weibo Wu, Qiyun Li* and Zhinan Zheng*

Volume 24, Issue 6, 2024

Published on: 21 November, 2023

Page: [629 - 641] Pages: 13

DOI: 10.2174/0115680096267203231024093601

Price: $65

Abstract

Background and Objectives: Preliminary experiments have revealed the abnormally high expression level of adropin in pancreatic ductal adenocarcinoma (PDA). This study investigated the role of adropin in the progression of PDA.

Methods: The paraffin-embedded samples of 20 patients with PDA were obtained from the hospital biobank, and immunohistochemistry was used to evaluate adropin expression. PDA cell lines were cultured and treated with recombinant adropin or adropin knockdown. Cell behavior was assessed, and the expression of phospho-vascular endothelial growth factor receptor (p-VEGFR2) and other related proteins was detected. The cell-derived xenograft (CDX) of PDA was established, and the effects of adropin or adropin knockdown on tumor growth were observed.

Results: The PDA cancer tissues exhibited elevated adropin protein expression compared with the paracancerous tissues, and the expression was positively correlated with carbohydrate antigen 19-9 levels in patients. Adropin significantly promoted the proliferation and migration of PDA cells and upregulated the expression of p-VEGFR2, Ki67, cyclin D1, and matrix metalloprotein 2 (MMP2). After the knockdown of adropin expression or blockade of VEGFR2, the above effects of adropin were significantly reversed. Adropin supplementation significantly accelerated tumor growth in PDA CDX; upregulated the expression of p-VEGFR2, Ki67, cyclin D1, and MMP2; and promoted angiogenesis in tumor tissue microenvironment. However, CDX inoculated with adropin knockdown cells produced the opposite results.

Conclusion: Adropin overexpression in PDA promotes cancer cell proliferation and angiogenesis in tumor microenvironment by continuously activating VEGFR2 signaling, thereby creating conditions for tumor progression. Thus, targeting adropin may be an effective anti-PDA strategy.

Keywords: Pancreatic ductal adenocarcinoma, adropin, VEGFR2, angiogenesis, cell-derived xenograft, paracancerous tissues.

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