Neutrophil elastase as a diagnostic marker and therapeutic target in colorectal cancers

Ai Sheng Ho, Chien Hsin Chen, Chun Chia Cheng, Chia Chi Wang, Hua Ching Lin, Tsai Yueh Luo, Gi Shih Lien, Jungshan Chang

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38 Citations (Scopus)

Abstract

Neutrophil elastase (NE), a serine protease secreted by neutrophils, contributes to the progression of cancers to enhance tumor invasion and metastasis. It has been well reported that the regions surrounding the colorectal cancerous tissues usually are decorated with increased accumulation or aggregation of neutrophils coupled with a higher deposition/expression of NE. Therefore, we hypothesized that an increased expressional level of NE in patients with colorectal cancer (CRC) may represent as one of putative biomarkers for CRC. The aim of this study was to evaluate and assure our hypothesis by measurements of the expressional level of NE in the sera and tissues from CRC patients. Moreover, we also proposed a potential therapeutic strategy by blocking enzymatic activity of NE using sivelestat to inhibit the progression of tumor developments. The infiltrated numbers of neutrophils from specimen tissues of CRC patients, and the secreted forms of NE in the sera were quantitatively measured and compared. To evaluate the serum NE as one of putative biomarkers of CRC patients, the receiver operating characteristic (ROC) curve was made to determine the cut-off value of NE in sera for assurance of CRC diagnosis. To evaluate NE as therapeutic target for CRC, sivelestat, a NE inhibitor, was used and administrated into the CRC xenografts. NE expression level coupled with tumor volume were measured and compared between the control and sivelestat-treated xenografts. We found that more infiltrated neutrophils and an increased NE expression were detected in the cancerous tissues compared to the normal tissues. The serum NE concentration in CRC patients was statistically higher than that in the healthy controls (0.56±0.08 μg/ml vs. 0.22±0.03μg/ml) (p

Original languageEnglish
Pages (from-to)473-480
Number of pages8
JournalOncotarget
Volume5
Issue number2
Publication statusPublished - 2014

Keywords

  • Biomarker
  • Colorectal cancer
  • Neutrophil elastase

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

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  • Cite this

    Ho, A. S., Chen, C. H., Cheng, C. C., Wang, C. C., Lin, H. C., Luo, T. Y., Lien, G. S., & Chang, J. (2014). Neutrophil elastase as a diagnostic marker and therapeutic target in colorectal cancers. Oncotarget, 5(2), 473-480.