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

J R Dunn1, J E Reed, D G du Plessis

  • 1JK Douglas Cancer Research Laboratories, Clatterbridge Hospital, Bebington, Wirral CH64 3JY, and Department of Neurological Science, University of Liverpool, UK. julie.dunn@ccrt.nhs.uk

British Journal of Cancer
|March 30, 2006
PubMed

Insights

ADAMTS-8, a protease with antiangiogenic properties, is highly expressed in normal brain tissue but significantly reduced in brain tumors. This suggests ADAMTS-8 may play a role in brain tumorigenesis and could be a therapeutic target.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Angiogenesis and extracellular matrix degradation are crucial for tumor progression.
  • Stromal-epithelial interactions and matrix composition are potential therapeutic targets for anti-cancer strategies.

Purpose of the Study:

  • To investigate the expression of ADAMTS-8, a protease with antiangiogenic properties, in normal brain tissues and brain tumors.
  • To explore the potential role of ADAMTS-8 in brain tumorigenesis and its regulation.

Main Methods:

  • Quantitative RT-polymerase chain reaction (PCR) to assess ADAMTS-8 mRNA expression in normal brain tissue and tumors.
  • Immunohistochemistry and Western analysis to evaluate ADAMTS-8 protein levels.
  • Methylation-specific PCR to investigate promoter hypermethylation as a mechanism for downregulation.

Main Results:

  • ADAMTS-8 exhibited high and equivalent expression in various normal brain regions.
  • A significant reduction in ADAMTS-8 mRNA was observed in all brain tumors compared to normal brain tissue, with undetectable levels in 41% of tumors and 100% of cell lines.
  • Downregulation of ADAMTS-8 protein was detected in over 77% of tumors.
  • Promoter hypermethylation was identified in a subset of brain tumors and glioma cell lines, suggesting an alternative downregulation mechanism.

Conclusions:

  • ADAMTS-8 expression is significantly reduced in brain tumors, indicating a potential role in brain tumorigenesis.
  • Further research is warranted to elucidate ADAMTS-8's function in regulating tumor angiogenesis and local invasion.
  • ADAMTS-8 represents a potential target for novel anti-invasive and antiangiogenic therapies in brain cancer.

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