Abstract
Decorin, a member of the small leucine-rich proteoglycans family, exists and plays multifunctional roles in stromal and epithelial cells. Emerging evidences showed that decorin is dysregulated expression in a wide variety of human tumors and affects a broad biology process of cancer cells, including growth, metastasis, and angiogenesis. Recent studies demonstrated that decorin could affect A549 proliferation though decreasing TGF-β1, cycling D1 expression and increasing P53 and P21 expression. However, limited data are available on the effect of decorin on metastasis of non-small-cell lung cancer (NSCLC) cell lines and how decorin impacts metastasis is still unknown. In this study, we identified decorin mRNA expression through Oncomine database and verified the expression of decorin mRNA and protein in 50 patients who underwent primary surgical resection of a NSCLC in the Department of Thoracic Surgery, Jinling Hospital, Nanjing University School of Medicine, China, between September 2013 and March 2014 by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot. Also, the correlationship between decorin and the NSCLC patients’ clinical characteristics or survival (www.kmplot.com) was analyzed. Via ectopic expression analyses and Western blot, the roles of decorin in proliferation, metastasis, and the underline mechanism for decorin expression were further explored. We found that decorin was downregulated in NSCLC tissues compared with the adjacent normal lung tissues or normal tissues. Additionally, the expression of decorin was correlated with tumor size, lymph node metastasis, tumor stage, and prognosis. We also showed that overexpression of decorin could inhibit NSCLC cell lines proliferation and metastasis. Through Western blot analysis, we identified that E-cadherin and vascular endothelial growth factor (VEGF) are two key factors responsible for the growth arrest and metastasis inhibition induced by decorin in NSCLC. Our results indicated that decorin plays crucial roles in NSCLC against carcinogenesis and progression. Decorin might be a predictive factor and an attractive therapeutic target for NSCLC patients.
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Abbreviations
- NSCLC:
-
Non-small-cell lung cancer
- ACS:
-
American Cancer Society
- ECM:
-
Extracellular matrix
- SLRPs:
-
Small leucine-rich repeat proteoglycans
- FBS:
-
Fetal bovine serum
- PMSF:
-
Phenylmethanesulfonyl fluoride
- OS:
-
Overall survival
- EMT:
-
Epithelial-mesenchymal transition
- VEGF:
-
Vascular endothelial growth factor
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Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (No. 81170064) and the Natural Science Foundation of China (No. 81302032). We apologize to all researchers whose relevant contributions were not cited due to space limitations.
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Shi, X., Liang, W., Yang, W. et al. Decorin is responsible for progression of non-small-cell lung cancer by promoting cell proliferation and metastasis. Tumor Biol. 36, 3345–3354 (2015). https://doi.org/10.1007/s13277-014-2968-8
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DOI: https://doi.org/10.1007/s13277-014-2968-8