Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours.

Abstract

Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal-epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protease with antiangiogenic properties, in brain tissues. Using quantitative RT-polymerase chain reaction (PCR), high, equivalent expression of ADAMTS-8 was found in normal whole brain, cerebral cortex, frontal lobe, cerebellum and meninges. ADAMTS-8 expression in 34 brain tumours (including 22 high-grade gliomas) and four glioma cell lines indicated at least two-fold reduction in mRNA compared to normal whole brain in all neoplastic tissues, and no detectable expression in 14 out of 34 (41%) tumours or four out of four (100%) cell lines. In contrast, differential expression of TSP1 and VEGF was seen in nine out of 15 (60%) and seven out of 13 (54%) tumours, with no relationship in the expression of these genes. Immunohistochemistry and Western analysis indicated downregulation of ADAMTS-8 protein in >77% tumours. Methylation-specific PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out of 24 brain tumours (a metastasis) and three out of four glioma cell lines suggesting an alternative mechanism of downregulation. These data suggest a role for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its role in regulation of tumour angiogenesis and local invasion.

• Authors: J R Dunn, J E Reed, D G du Plessis, E J Shaw, P Reeves, A L Gee, P Warnke, C Walker
• Journal: British journal of cancer (Br J Cancer) Vol. 94 Issue 8 Pg. 1186-93 (Apr 24 2006) ISSN: 0007-0920 [Print] England
• PMID: 16570050 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Cell Cycle Proteins
• RNA, Messenger
• TSPY1 protein, human
• Vascular Endothelial Growth Factor A
• ADAM Proteins
• ADAMTS Proteins
• ADAMTS8 protein, human

Topics

• ADAM Proteins (genetics, metabolism, pharmacology)
• ADAMTS Proteins
• Angiogenesis Inhibitors (genetics, metabolism, pharmacology)
• Binding Sites
• Blotting, Western
• Brain Neoplasms (metabolism)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• Down-Regulation
• Gene Expression Profiling
• Humans
• Methylation
• Promoter Regions, Genetic
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sensitivity and Specificity
• Vascular Endothelial Growth Factor A (genetics, metabolism)