Abstract
Objective
This study aimed to confirm that biglycan (BGN) can promote the migration and invasion in endometrial cancer both in vitro and in vivo and the possible therapeutic value of BGN in endometrial cancer.
Methods
Western blot was used to screen out the higher protein level of BGN in human endometrial cancer cells; BGN knocked down cells were constructed by lentiviral transfection; The effect of BGN in endometrial cancer detected by wound healing, transwell migration, and invasion, endothelial tube formation assay in vitro, and xenograft model in vivo.
Results
(1) We found that BGN expression level is higher in the Ishikawa (ISK, high differentiation) and AN3CA (poor differentiation) cells than other endometrial cancer cells. (2) BGN enhances endometrial cancer cell wound healing, invasion, and migration ability and formation ability of endothelial cells in vitro. Xenograft model has confirmed the outcome in vivo.
Conclusions
BGN might play an important role on metastasis in human endometrial cancer and it might be a target marker for the molecular therapy of advanced and recurrence endometrial cancer.
Similar content being viewed by others
References
Siegel R, Ma J, Zou Z et al (2014) Cancer statistics, 2014. CA Cancer J Clin 64(1):9–29
Loukovaara M, Luomaranta A, Leminen A (2013) Treatment of endometrial carcinoma. Duodecim; laaketieteellinen aikakauskirja 130(22–23):2348–2355
Frantz C, Stewart KM, Weaver VM (2010) The extracellular matrix at a glance. J Cell Sci 123(24):4195–4200
Weber CK, Sommer G, Michl P et al (2001) Biglycan is overexpressed in pancreatic cancer and induces G1-arrest in pancreatic cancer cell lines. Gastroenterology 121(3):657–667
Fisher LW, Heegaard AM, Vetter U et al (1991) Human biglycan gene. Putative promoter, intron-exon junctions, and chromosomal localization. J Biol Chem 266(22):14371–14377
Wadhwa S, Embree MC, Bi Y et al (2004) Regulation, regulatory activities, and function of biglycan. Crit Rev Eukaryot Gene Expr 14(4):301–315
Gotte M, Feugaing DDS, Kresse H (2004) Biglycan is internalized via a chlorpromazine-sensitive route. Cell Mol Biol Lett 9(3):475–482
Aprile G, Avellini C, Reni M et al (2013) Biglycan expression and clinical outcome in patients with pancreatic adenocarcinoma. Tumor Biology 34(1):131–137
Mikula M, Rubel T, Karczmarski J et al (2011) Integrating proteomic and transcriptomic high-throughput surveys for search of new biomarkers of colon tumors. Funct Integr Genomics 11(2):215–224
Pan S, Cheng L, White JT et al (2009) Quantitative proteomics analysis integrated with microarray data reveals that extracellular matrix proteins, catenins, and p53 binding protein 1 are important for chemotherapy response in ovarian cancers. OMICS 13(4):345–354
Nishino R, Honda M, Yamashita T et al (2008) Identification of novel candidate tumour marker genes for intrahepatic cholangiocarcinoma. J Hepatol 49(2):207–216
Hu L, Duan Y, Li J et al (2014) Biglycan enhances gastric cancer invasion by activating FAK signaling pathway. Oncotarget 5(7):1885
Liu Y, Li W, Li X et al (2014) Expression and significance of biglycan in endometrial cancer. Arch Gynecol Obstet 289(3):649–655
Zhu YH, Yang F, Zhang SS et al (2013) High expression of biglycan is associated with poor prognosis in patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol 6(11):2497
Jaeger J, Koczan D, Thiesen HJ et al (2007) Gene expression signatures for tumor progression, tumor subtype, and tumor thickness in laser-microdissected melanoma tissues. Clinical cancer research 13(3):806–815
Niedworok C, Röck K, Kretschmer I et al (2013) Inhibitory role of the small leucine-rich proteoglycan biglycan in bladder cancer. PLoS One 8(11):e80084
Merline R, Moreth K, Beckmann J et al (2011) Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and MicroRNA-21. Science Signaling 4(199):ra75–ra75
Chen WB, Lenschow W, Tiede K et al (2002) Smad4/DPC4-dependent regulation of biglycan gene expression by transforming growth factor-β in pancreatic tumor cells. J Biol Chem 277(39):36118–36128
Li Q (2014) Transforming growth factor β signaling in uterine development and function. J Animal Sci Biotechnol 5(1):52
Loomans HA, Andl CD (2014) Intertwining of activin a and TGF-β signaling: dual roles in cancer progression and cancer cell invasion. Cancers 7(1):70–91
Brown S, Teo A, Pauklin S et al (2011) Activin/Nodal signaling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitors. Stem Cells 29(8):1176–1185
Jones KL, de Kretser DM, Patella S et al (2004) Activin A and follistatin in systemic inflammation. Mol Cell Endocrinol 225(1):119–125
Faure S, Lee MA, Keller T et al (2000) Endogenous patterns of TGFbeta superfamily signaling during early Xenopus development. Development 127(13):2917–2931
Burdette JE, Jeruss JS, Kurley SJ et al (2005) Activin A mediates growth inhibition and cell cycle arrest through Smads in human breast cancer cells. Cancer Res 65(17):7968–7975
Galamb O, Sipos F, Spisák S et al (2009) Potential biomarkers of colorectal adenoma–dysplasia–carcinoma progression: mRNA expression profiling and in situ protein detection on TMAs reveal 15 sequentially upregulated and 2 downregulated genes. Anal Cell Pathol 31(1):19–29
Gallagher J (2007) Messages in the matrix: proteoglycans go the distance. Dev Cell 13(2):166–167
Yamamoto K, Ohga N, Hida Y et al (2012) Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells. Br J Cancer 106(6):1214–1223
Yamamoto K, Ohga N, Hida Y et al (2012) Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells. Br J Cancer 106(6):1214–1223
Berendsen AD, Pinnow EL, Maeda A et al (2014) Biglycan modulates angiogenesis and bone formation during fracture healing. Matrix Biol 35:223–231
Schaefer L, Babelova A, Kiss E et al (2005) The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. Journal of Clinical Investigation 115(8):2223
Babelova A, Moreth K, Tsalastra-Greul W et al (2009) Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors. J Biol Chem 284(36):24035–24048
Tufvesson E, Westergren-Thorsson G (2003) Biglycan and decorin induce morphological and cytoskeletal changes involving signalling by the small GTPases RhoA and Rac1 resulting in lung fibroblast migration. J Cell Sci 116(23):4857–4864
Theocharis AD, Skandalis SS, Neill T et al (2015) Insights into the key roles of proteoglycans in breast cancer biology and translational medicine. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer
Schaefer L, Beck KF, Raslik I et al (2003) Biglycan, a nitric oxide-regulated gene, affects adhesion, growth, and survival of mesangial cells. J Biol Chem 278(28):26227–26237
Acknowledgments
This study was partly funded by the National Natural Science Foundation of China [81072121, 81372808 (J.J.)] and [81173614 (Q.T.L)], and was also partly funded by the Science and Technology Development planning of Shandong [2012G0021823 (J.J)] and [2011GSF12122 (X.Z and J.J)] and the Technology Developing Planning of Jinan (201303035).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
We declare that we have no conflict of interest with other people or organizations. All authors have contributed significantly to this work and are in agreement with the content of the manuscript.
Rights and permissions
About this article
Cite this article
Sun, H., Wang, X., Zhang, Y. et al. Biglycan enhances the ability of migration and invasion in endometrial cancer. Arch Gynecol Obstet 293, 429–438 (2016). https://doi.org/10.1007/s00404-015-3844-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00404-015-3844-5