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.
Mentioned Articles
Bagci-Onder T, Agarwal A, Flusberg D, Wanningen S, Sorger P, Shah K.
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.
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