A review of the role of stem cells in the development and treatment of glioma.

The neurosurgical management of patients with intrinsic glial cancers is one of the most rapidly evolving areas of practice. This has been fuelled by advances in surgical technique not only in cytoreduction but also in drug delivery. Further innovation will depend on a deeper understanding of the biology of the disease and an appreciation of the limitations of current knowledge. Here we review the controversial topic of cancer stem cells applied to glioma to provide neurosurgeons with a working overview. It is now recognised that the adult human brain contains regionally specified cell populations capable of self-renewal that may contribute to tumour growth and maintenance following accumulated mutational change. Tumour cells adapted to maintain growth demonstrate some stem-like characteristics and as such constitute a legitimate therapeutic target. Cellular reprogramming technologies raise the potential of developing stem cells as novel surgical tools to target disease and possibly ameliorate some of the consequences of treatment. Achieving these goals remains a significant challenge to neurosurgical oncologists, not least in challenging how we think about treating brain cancer. This review will briefly examine our understanding of adult stem cells within the brain, the evidence that they contribute to the development of brain tumours as tumour-initiating cells, and the potential implications for therapy. It will also look at the role stem cells may play in the future management of glioma.

Glioblastoma cell lines derived under serum-free conditions can be used as an in vitro model system to evaluate therapeutic response.

We provide evidence that six glioblastoma cell lines derived and maintained under serum-free conditions secrete VEGF and four also expressed VEGF(R2). Expression of VEGF(R2) was associated with reduced proliferation in response to anti-VEGF antibodies. Spontaneous loss of VEGF(R2) over passage was associated with loss of this anti-proliferative effect. Gain of expression of VEGF(R2) was not associated with the acquisition of responsiveness to anti-VEGF antibodies. Secretion of PDGF was absent in 5/6 of our cell lines and none of the cell lines had reduced proliferation in response to anti-PDGF antibodies suggesting that PDGF autocrine signalling was unlikely to be significant in tumour proliferation. These data are consistent with published clinical trials suggesting that glioblastoma cell lines derived under serum-free conditions have the potential for use in drug screening and individualising patient therapy.