Glioblastoma

Blockage of Ca2+-permeable AMPA receptors suppresses migration and induces apoptosis in human glioblastoma cells.Ishiuchi, S. et al. Nature Med. 12 Aug 2002 (doi:10.1038/nm746)

Glioblastoma multiforme is highly invasive and difficult to treat. Glioblastoma cells express Ca2+-permeable AMPA-type glutamate receptors that are involved in the migration response. Their overexpression resulted in migration and proliferation, and their conversion to Ca2+-impermeable receptors inhibited cell migration and induced apoptosis. So, inhibition of these receptors might prevent glioblastoma invasion.

Cell Migration

Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling.Avizienyte, E. et al. Nat Cell Biol. 4, 632–638 (2002)

Src activity is elevated in colon cancer, but what is its effect? Increased Src activity results in the redistribution of components of adherens junctions to integrin–adhesion complexes in the presence of high calcium levels. E-cadherin remains internalized, so cannot assemble the correct intercellular contacts. A Src mutant that lacks the kinase domain does not deregulate E-cadherin. So, expression of catalytically active Src might facilitate cancer-cell migration.

Epidemiology

Risk of cancer in patients with human pituitary growth hormone in the UK, 1959-85: a cohort study.Swerdlow, A. J. et al. Lancet 360, 273–277 (2002)

Growth hormone raises serum concentrations of insulin-like growth factor 1 (IGF-1), and raised levels of growth hormone and IGF-1 might be associated with an increased risk of certain solid cancers. Follow-up of nearly 2,000 patients who were treated during childhood with human pituitary growth hormone showed a significant increase in the risk of developing colorectal cancer and Hodgkin's disease. This was based on small numbers of cancer cases, but the findings are nevertheless of concern and warrant further investigation.

Therapeutics

Inhibition of glioma growth by tumor-specific activation of double-stranded RNA-dependent protein kinase PKR.Shir, A. & Levitzki, A. Nature Biotechnol. 19 Aug 2002 (doi:10.1038/nbt730)

A new antisense RNA strategy selectively targets tumour cells. Antisense RNAs that are complementary to sequences that flank a deletion or translocation bind the mutant RNAs to produce a double-stranded molecule. These molecules activate a double-stranded RNA-dependent protein kinase (PKR), which signals cells to undergo apoptosis. A lentiviral vector expressing a 39-nucleotide antisense RNA that is complementary to the flanking regions of an epidermal-growth-factor receptor (EGFR) gene deletion was shown to activate PKR, causing glioblastoma cells to undergo apoptosis.