Some cancers are particularly difficult to treat, particularly brain tumours. Glioblastoma is an aggressive form of cancer in the brain which, although responds initially to treatment, is refractory and often always fatal. Treating cancerous cells with a protein called TRAIL is a specific treatment which causes cancer cell death in around 50% of cancer cell lines. Bagci-Onder et al. employ some interesting molecular techniques to studying the effect of TRAIL on glioblastoma cell viability.
Neuronal stem cells were used to deliver soluble TRAIL protein to glioblastoma cells and the way in which this happens was modelled by artificially colouring both cell types and watching their interactions when grown together. Two out of three glioblastoma cell lines tested were sensitive to TRAIL treatment and underwent a form of highly controlled cell death called apoptosis.
The killing of these cells by TRAIL treatment was dependent on the levels of two proteins on the cell surface called death receptors; death receptor 4 (DR4) and death receptor (DR5). The group observed that the higher the levels of these receptors, the more receptive to TRAIL treatment the cells were. This led the group to postulate that increasing death receptor expression could enhance the effectiveness of TRAIL in treating glioblastoma.
To see how they could increase death receptor expression in cancerous cells, the group used a panel of different drugs known to affect the way cells function. They found that targeting histone deacetylases (HDACs) [see previous post] with a drug called MS-275 caused an increase in death receptor levels at the surface of cells. As expected, this also led to an increased sensitivity to TRAIL treatment. Importantly, the one glioblastoma cell line which was initially resistant to TRAIL treatment became sensitive to the killing power of TRAIL if cells were also treated with MS-275. This study highlights a potential new combination treatment for glioblastoma.
Bagci-Onder T, Agarwal A, Flusberg D, Wanningen S, Sorger P, Shah K.
Real-time imaging of the dynamics of death receptors and therapeutics that overcome TRAIL resistance in tumors.
Oncogene. 2013 Jun 6;32(23):2818-27. doi: 10.1038/onc.2012.304. Epub 2012 Jul 23.
"Types of primary brain tumours : Cancer Research UK : CancerHelp UK." Cancer Research UK: the UK's leading cancer charity : Cancer Research UK . N.p., n.d. Web. 13 June 2013.