The University of Southampton
Centre for Human Development, Stem Cells and RegenerationResearch themes

Brain tumour stem cell regulation

Clonal spheres grown from glioblastoma samples obtained from patients during their operative procedure, after informed consent was collected
Clonal Spheres

For most brain tumours, cure is not currently possible and recurrence is common. Treatment failure may result from a key cell type persistence after treatment - brain tumour stem cells (BTSCs). The recurrence rate of glial tumours may be due to the BTSC survival and subsequent motility leading to brain infiltration. Using glioblastoma samples obtained from patients during their operative procedure, we showed upregulation of ADAM10/17 in brain tumour tissue and stem cells. ADAMs (A disintegrin and metalloproteinases) are proteins involved in proteolysis and cell adhesion, which promote the progression of several solid cancers.

We also showed that the self-renewal of brain tumour stem cells is altered by ADAMs inhibition. This highlights the potential effect ADAM inhibition could have on brain tumour growth. We are currently investigating the cellular and molecular mechanism behind this effect. This will bring further understanding of the biological mechanisms regulating brain tumour development and identify potential therapeutic targets.

Current investigations point towards an important role of BTSC migration and invasion potentials. We are investigating what are these potentials and how migration and invasion of BTSCs can be regulated. Our preliminary data suggest a critical role for ADAM10/17 in BTSC chemotaxis. By identifying the mechanism(s) involved in this function, we will not only elucidate a novel signalling pathway in brain tumour invasion, but identify novel and more specific therapeutic targets.

Cells migrating out of a brain tumour sphere when on adhesive substrate
Migrating cells

People

Sandrine Willaime-Morawek, Elodie Siney, William Gray

Publications

Bulstrode et al (2012) A-Disintegrin and Metalloprotease (ADAM) 10 and 17 Promote Self-renewal of Brain Tumor Sphere Forming Cells. Cancer Letters, in press

Funding

The Royal Society, Wessex Medical Trust, University of Southampton Faculty of Medicine, University Hospital Southampton R&D, MRC Capacity building studentship, The Nuffield Foundation

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