RUNX3 expression is lost in glioma and its restoration causes drastic suppression of tumor invasion and migration
- 430 Downloads
The aim of this study is to investigate whether the expression of RUNX3 is related to the development of glioma, and the role of RUNX3 in glioma cells growth, invasion and migration.
We analyzed the protein expression of RUNX3 by immunohistochemistry in 188 glioma tissues, 8 normal brain tissues and 8 tumor adjacent normal brain tissues using tissue microarray technique. We studied whether RUNX3 restoration can suppress glioma cells growth, invasion and migration by performing MTT cell proliferation assay, matrigel cell invasion assay, wound-healing assay and migration assay. We also detected MMP-2 protein expression and enzyme activity by western blot analysis and gelatin zymography.
We found that RUNX3 expression was decreased in benign tumor and malignant tumor compared with tumor adjacent normal brain tissue (P < 0.01 and P < 0.05, respectively). We did not find any correlation between RUNX3 expression and clinicopathological parameters. In addition, we demonstrated that re-expression of RUNX3 in glioma cells resulted in significantly inhibited cell invasion and migration abilities. This reduced cell invasion and migration abilities were due to MMP-2 protein expression and enzyme activity suppression after RUNX3 restoration.
Our data indicated that RUNX3 expression is significantly decreased in human glioma, and targeting of the RUNX3 pathway may constitute a potential treatment modality for glioma.
KeywordsRUNX3 Glioma Tissue microarray Invasion Migration
This project is supported by grants from the National Natural Science Foundation of China (No. 30972976, 81071854), the Program for New Century Excellent Talents in University (NCET-08-0700) and Xuzhou Medical College (No. 2010KJZ03).
Conflict of interest
We declare that we have no conflict of interest.
- Ahlquist T, Lind GE, Costa VL, Meling GI, Vatn M, Hoff GS, Rognum TO, Skotheim RI, Thiis-Evensen E, Lothe RA (2008) Gene methylation profiles of normal mucosa, and benign and malignant colorectal tumors identify early onset markers. Mol Cancer 7:94. doi: 10.1186/1476-4598-7-94 PubMedCrossRefGoogle Scholar
- Guan H, Cai J, Zhang N, Wu J, Yuan J, Li J, Li M (2011) Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome. Int J Cancer. doi: 10.1002/ijc.26049
- Ichimura K, Vogazianou AP, Liu L, Pearson DM, Backlund LM, Plant K, Baird K, Langford CF, Gregory SG, Collins VP (2008) 1p36 is a preferential target of chromosome 1 deletions in astrocytic tumours and homozygously deleted in a subset of glioblastomas. Oncogene 27(14):2097–2108. doi: 10.1038/sj.onc.1210848 PubMedCrossRefGoogle Scholar
- Javed A, Barnes GL, Pratap J, Antkowiak T, Gerstenfeld LC, van Wijnen AJ, Stein JL, Lian JB, Stein GS (2005) Impaired intranuclear trafficking of Runx2 (AML3/CBFA1) transcription factors in breast cancer cells inhibits osteolysis in vivo. Proc Natl Acad Sci USA 102(5):1454–1459. doi: 10.1073/pnas.0409121102 PubMedCrossRefGoogle Scholar
- Lau QC, Raja E, Salto-Tellez M, Liu Q, Ito K, Inoue M, Putti TC, Loh M, Ko TK, Huang C, Bhalla KN, Zhu T, Ito Y, Sukumar S (2006) RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Cancer Res 66(13):6512–6520. doi: 10.1158/0008-5472.CAN-06-0369 PubMedCrossRefGoogle Scholar
- Li QL, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae SC, Ito Y (2002) Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 109(1):113–124PubMedCrossRefGoogle Scholar
- Pennison M, Pasche B (2007) Targeting transforming growth factor-beta signaling. Curr Opin Oncol 19(6):579–585. doi: 10.1097/CCO.0b013e3282f0ad0e00001622-200711000-00007 PubMedCrossRefGoogle Scholar