Astrocyte Elevated Gene-1: A Novel Target for Human Glioma Therapy

Strategic Insights -

Malignant gliomas, including glioblastoma multiforme (GBM) and anaplastic astrocytomas, are the most common primary brain tumors. Despite multimodal treatment including surgery, chemotherapy, and radiation, median survival for patients with GBMs is only 12 to 15 months. Identifying molecules critical for glioma progression is crucial for devising effective targeted therapy. Researchers have investigated the potential contribution of astrocyte elevated gene-1 (AEG-1) in gliomagenesis and explored the possibility of AEG-1 as a therapeutic target for malignant glioma.

Key Takeaways:

  • AEG-1 expression was significantly elevated in 90% of diverse human brain tumor samples, including GBMs and astrocytic tumors, compared to normal brain tissues and normal astrocytes.
  • Knockdown of AEG-1 by small interfering RNA inhibited cell viability, cloning efficiency, and invasive ability of U87 human glioma cells and 9L rat gliosarcoma cells.
  • Matrix metalloproteases (MMP-2 and MMP-9) are involved in AEG-1-mediated invasion of glioma cells, as researchers found that MMP-2 and MMP-9 were highly expressed in AEG-1 overexpressing glioma cells.
  • In an orthotopic nude mouse brain tumor model using primary human GBM12 tumor cells, AEG-1 small interfering RNA significantly suppressed glioma cell growth in vivo.
  • The researchers concluded that AEG-1 may play a crucial role in the pathogenesis of glioma, and that AEG-1 could represent a viable potential target for malignant glioma therapy.
  • The study was conducted by L. Emdad and colleagues from the Mount Sinai School of Medicine, Department of Neurosurgery and Oncological Sciences.

Statistics:

  • Median survival for patients with GBMs is only 12 to 15 months despite multimodal treatment.
  • 90% of diverse human brain tumor samples showed significantly elevated AEG-1 expression.
  • 9 normal brain tissues and 98 brain tumor patient samples were analyzed by Western blot analysis and immunohistochemistry.
  • Inhibition of AEG-1 expression by small interfering RNA resulted in a 70% reduction in cell viability in U87 human glioma cells.
  • Glioma cell growth was suppressed by 30% in an orthotopic nude mouse brain tumor model using primary human GBM12 tumor cells.

Sources:

  • Molecular Cancer Therapeutics (Astrocyte elevated gene-1: a novel target for human glioma therapy. Molecular Cancer Therapeutics, 2010;9(1):79-88)
  • Brain Cancer Gene Therapy
  • NewsRx.com (Cancer Gene Therapy Week editors, 2010)