The online version of this article (https://doi.org/10.1186/s12885-017-3962-5) contains supplementary material, which is available to authorized users.
One of the major challenges in soft tissue sarcomas is to identify factors that predict metastasis. AZGP1 is a potential biomarker of cancer progression, but its value in soft tissue sarcomas remains unknown. The aim of this study is to determine the expression level of AZGP1 in soft tissue sarcomas, and to analyze its influence on tumor progression.
AZGP1 immunohistochemistry (IHC) and RT-PCR were performed in 86 patients with soft tissue sarcomas. The relationships between AZGP1 levels and clinicopathologic features were analyzed. In vitro experiments were performed using fibrosarcoma (HT1080), rhabdomyosarcoma (RD) and synovial sarcoma (SW982) cell lines to corroborate our findings. We used lentiviral over-expression and knockdown assays to examine how changes of AZGP1 expressions might affect cellular migration and invasion.
The quantitative RT-PCR results showed that AZGP1 expression was negatively correlated with metastasis and overall survival in soft tissue sarcomas (p < 0.05). Immunohistochemical staining showed lower expression of AZGP1 in patients with metastasis than in those without. Kaplan-Meier survival analysis showed that patients with low expression of AZGP1 had shorter overall (p = 0.056) and metastasis-free survivals (p = 0.038). These findings were corroborated by our in vitro experiments. Over-expression of AZGP1 significantly decreased RD cellular migration and invasion by 64% and 78%, respectively. HT1080 cells migration was inhibited by 2-fold, whereas their invasion was repressed by 7-fold after AZGP1 knockdown.
Our study reveals that reduced AZGP1 expression correlates with in vitro cellular migration and invasion. In vivo, it is associated with higher metastatic risk and shorter survival in patients with soft tissue sarcomas.
Additional file 1: Table S1. Primers sequence. The primer names and sequence for Q-PCR analysis of ZAG and recombinant plasmid construct were listed in the table. (DOC 34 kb)12885_2017_3962_MOESM1_ESM.doc
Nicolazzo C, Gradilone A. Significance of circulating tumor cells in soft tissue sarcoma. Anal Cell Pathol. 2015;2015:697395. CrossRef
Huang YLL, Zhang CZ, Yi C, Liu LL, Zhou X, Xie GB, Cai MY, Li Y, Yun JP. Decreased expression of zinc-alpha2-glycoprotein in hepatocellular carcinoma associates with poor prognosis. J Transl Med. 2012;24(10):106–15. CrossRef
Xue Y, Yu F, Yan D, Cui F, Tang H, Wang X, Chen J, Lu H, Zhao S, Peng Z. Zinc-alpha-2-glycoprotein: a candidate biomarker for colon cancer diagnosis in Chinese population. Int J Mol Sci. 2015;16(1):691–703. CrossRef
Burdelski C, Kleinhans S, Kluth M, Hube-Magg C, Minner S, Koop C, Graefen M, Heinzer H, Tsourlakis MC, Wilczak W, et al. Reduced AZGP1 expression is an independent predictor of early PSA recurrence and associated with ERG-fusion positive and PTEN deleted prostate cancers. Int J Cancer. 2016;138(5):1199–206. CrossRefPubMed
Albertus DLSC, Chen G, Wang X, Hartojo W, Lin L, Silvers A, Thomas DG, Giordano TJ, Chang AC, Orringer MB, Bigbee WL, Chinnaiyan AM, Beer DG. AZGP1 autoantibody predicts survival and histone deacetylase inhibitors increase expression in lung adenocarcinoma. J Thorac Oncol. 2008;3(11):1236–44. CrossRefPubMed
He NBH, Tyring SK, Ohkubo I, Brysk MM. Zinc-alpha(2)-glycoprotein hinders cell proliferation and reduces cdc2 expression. J Cell Biochem Suppl. 2001;suppl36(2):162–9. CrossRef
Kong B, Michalski CW, Hong X, Valkovskaya N, Rieder S, Abiatari I, Streit S, Erkan M, Esposito I, Friess H, et al. AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-beta-mediated ERK signaling. Oncogene. 2010;29(37):5146–58. CrossRefPubMed
Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796(2):75–90. PubMed
- AZGP1 inhibits soft tissue sarcoma cells invasion and migration
Marc El Beaino
- BioMed Central
Neu im Fachgebiet Onkologie
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