Abstract
Emerging evidences have shown that decorin expression is significantly reduced in many cancer tissues and cancer cells. However, its biological role and clinical significance in cholangiocarcinoma development and progression are unknown. In this study, immunohistochemistry was conducted to investigate the expression of decorin in cholangiocarcinomas. The results showed that decorin levels markedly decreased in 44 cholangiocarcinoma tissues compared to 40 adjacent normal tissues. The analysis between decorin expression and clinicopathological characteristics in cholangiocarcinoma patients showed that patients with low levels of decorin expression had a relatively poor prognosis. Moreover, recombinant human decorin treatment and overexpression of decorin in cholangiocarcinoma cells could inhibit cell proliferation, migration, and invasion and promote apoptosis. Furthermore, the E-cadherin expression significantly increased after decorin overexpression or use of recombinant human decorin in cholangiocarcinoma cells. Our findings indicated that downregulation of decorin may be identified as a poor prognostic biomarker in cholangiocarcinomas. Also, decorin-mediated inhibition of cholangiocarcinoma cell growth, migration, and invasion and promotion of cell apoptosis might be through regulation of the expression of E-cadherin in vitro.
Similar content being viewed by others
References
Olnes MJ, Erlich R. A review and update on cholangiocarcinoma. Oncol Basel. 2004;66:167–79. doi:10.1159/000077991.
Sripa B, Pairojkul C. Cholangiocarcinoma: lessons from Thailand. Curr Opin Gastroenterol. 2008;24:349–56. doi:10.1097/MOG.0b013e3282fbf9b3.
Vauthey JN, Blumgart LH. Recent advances in the management of cholangiocarcinomas. Semin Liver Dis. 1994;14:109–14. doi:10.1055/s-2007-1007302.
Nimura Y. Radical surgery: vascular and pancreatic resection for cholangiocarcinoma. HPB (Oxford). 2008;10:183–5. doi:10.1080/13651820801992682.
Khan SA, Taylor-Robinson SD, Toledano MB, Beck A, Elliott P, Thomas HC. Changing international trends in mortality rates for liver, biliary and pancreatic tumours. J Hepatol. 2002;37:806–13.
Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma. Lancet. 2005;366:1303–14. doi:10.1016/S0140-6736(05)67530-7.
de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM. Biliary tract cancers. N Engl J Med. 1999;341:1368–78. doi:10.1056/NEJM199910283411807.
Dokduang H, Juntana S, Techasen A, Namwat N, Yongvanit P, Khuntikeo N, et al. Survey of activated kinase proteins reveals potential targets for cholangiocarcinoma treatment. Tumour Biol. 2013. doi:10.1007/s13277-013-0930-9.
Iozzo RV, Moscatello DK, McQuillan DJ, Eichstetter I. Decorin is a biological ligand for the epidermal growth factor receptor. J Biol Chem. 1999;274:4489–92.
Reed CC, Iozzo RV. The role of decorin in collagen fibrillogenesis and skin homeostasis. Glycoconj J. 2002;19:249–55. doi:10.1023/A:1025383913444.
Hamid AS, Li J, Wang Y, Wu X, Ali HA, Du Z, et al. Recombinant human decorin upregulates p57KIP2 expression in HepG2 hepatoma cell lines. Mol Med Rep. 2013;8:511–6. doi:10.3892/mmr.2013.1510.
Toole BP. Solubility of collagen fibrils formed in vitro in the presence of sulphated acid mucopolysaccharide–protein. Nature. 1969;222:872–3.
Stander M, Naumann U, Wick W, Weller M. Transforming growth factor-beta and p-21: multiple molecular targets of decorin-mediated suppression of neoplastic growth. Cell Tissue Res. 1999;296:221–7.
Bi X, Pohl NM, Qian Z, Yang GR, Gou Y, Guzman G, et al. Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice. Carcinogenesis. 2012;33:326–30. doi:10.1093/carcin/bgr293.
Santra M, Skorski T, Calabretta B, Lattime EC, Iozzo RV. De novo decorin gene expression suppresses the malignant phenotype in human colon cancer cells. Proc Natl Acad Sci U S A. 1995;92:7016–20.
Troup S, Njue C, Kliewer EV, Parisien M, Roskelley C, Chakravarti S, et al. Reduced expression of the small leucine-rich proteoglycans, lumican, and decorin is associated with poor outcome in node-negative invasive breast cancer. Clin Cancer Res. 2003;9:207–14.
De Luca A, Santra M, Baldi A, Giordano A, Iozzo RV. Decorin-induced growth suppression is associated with up-regulation of p21, an inhibitor of cyclin-dependent kinases. J Biol Chem. 1996;271:18961–5.
Campioni M, Ambrogi V, Pompeo E, Citro G, Castelli M, Spugnini EP, et al. Identification of genes down-regulated during lung cancer progression: a cDNA array study. J Exp Clin Cancer Res. 2008;27:38. doi:10.1186/1756-9966-27-38.
Goldoni S, Seidler DG, Heath J, Fassan M, Baffa R, Thakur ML, et al. An antimetastatic role for decorin in breast cancer. Am J Pathol. 2008;173:844–55. doi:10.2353/ajpath.2008.080275.
Bi X, Tong C, Dockendorff A, Bancroft L, Gallagher L, Guzman G, et al. Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis. 2008;29:1435–40. doi:10.1093/carcin/bgn141.
Hsu SM, Raine L. Protein A, avidin, and biotin in immunohistochemistry. J Histochem Cytochem. 1981;29:1349–53.
Iozzo RV, Chakrani F, Perrotti D, McQuillan DJ, Skorski T, Calabretta B, et al. Cooperative action of germ-line mutations in decorin and p53 accelerates lymphoma tumorigenesis. Proc Natl Acad Sci U S A. 1999;96:3092–7.
Kresse H, Hausser H, Schonherr E. Small proteoglycans. Experientia. 1993;49:403–16.
Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV. Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol. 1997;136:729–43.
Chakravarti S, Magnuson T, Lass JH, Jepsen KJ, LaMantia C, Carroll H. Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J Cell Biol. 1998;141:1277–86.
Zhu JX, Goldoni S, Bix G, Owens RT, McQuillan DJ, Reed CC, et al. Decorin evokes protracted internalization and degradation of the epidermal growth factor receptor via caveolar endocytosis. J Biol Chem. 2005;280:32468–79. doi:10.1074/jbc.M503833200.
Schonherr E, Sunderkotter C, Iozzo RV, Schaefer L. Decorin, a novel player in the insulin-like growth factor system. J Biol Chem. 2005;280:15767–72. doi:10.1074/jbc.M500451200.
Guidetti GF, Bartolini B, Bernardi B, Tira ME, Berndt MC, Balduini C, et al. Binding of von Willebrand factor to the small proteoglycan decorin. Febs Lett. 2004;574:95–100. doi:10.1016/j.febslet.2004.08.011.
Schmalhofer O, Brabletz S, Brabletz T. E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 2009;28:151–66. doi:10.1007/s10555-008-9179-y.
Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science. 2004;303:1483–7. doi:10.1126/science.1094291.
Hermiston ML, Wong MH, Gordon JI. Forced expression of E-cadherin in the mouse intestinal epithelium slows cell migration and provides evidence for nonautonomous regulation of cell fate in a self-renewing system. Genes Dev. 1996;10:985–96.
Oka H, Shiozaki H, Kobayashi K, Inoue M, Tahara H, Kobayashi T, et al. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 1993;53:1696–701.
Derksen PW, Liu X, Saridin F, van der Gulden H, Zevenhoven J, Evers B, et al. Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell. 2006;10:437–49. doi:10.1016/j.ccr.2006.09.013.
Wheelock MJ, Johnson KR. Cadherins as modulators of cellular phenotype. Annu Rev Cell Dev Biol. 2003;19:207–35. doi:10.1146/annurev.cellbio.19.011102.111135.
Acknowledgments
The authors thank the National Natural Science Foundation of China (grant nos. 30972910 and 81172269), the Natural Science Foundation of Jiangsu Province (grant no. SBK201123832), the Postdoctoral Science Foundation of China (grant no. 20060390294), and the Key Project Research Fund of Nanjing Medical University (grant no. 2011NJMU246).
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding authors
Additional information
Xiang Yu and Yanfen Zou contributed equally to this work and should be regarded as joint first authors.
Rights and permissions
About this article
Cite this article
Yu, X., Zou, Y., Li, Q. et al. Decorin-mediated inhibition of cholangiocarcinoma cell growth and migration and promotion of apoptosis are associated with E-cadherin in vitro. Tumor Biol. 35, 3103–3112 (2014). https://doi.org/10.1007/s13277-013-1402-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-013-1402-y