The Wnt Signaling Pathway in Glioblastoma Stem Cells

Background
Glioblastoma is the most frequently occurring brain tumor, and one of the most aggressive of all human cancers. Median survival has not changed for decades and is approximately 12 months despite aggressive surgery, radiation and chemotherapy. More effective treatments are therefore desperately sought.

We and others believe that the failure of current treatment of chemotherapy and irradiation, as well as the diffuse invasion of the brain prior to surgery, could be explained by the existence of tumor cells with stem cell properties – glioblastoma stem cells (GSCs).

Cecilie Sandberg in our group has therefore compared gene expression in NSCs and GSCs using microarray analysis (29.000 genes) and real-time PCR (96 genes). This has identified differential gene expression in 14 different cell signaling pathways, and of these the Wnt pathway emerged as the most interesting to study further.

The Wnt Signaling Pathway
The Wnt pathway is highly conserved among eukaryotes and regulates diverse processes including cell proliferation, differentiation, polarity, and migration, which are all fundamental to embryogenesis. Additionally, deregulation of Wnt signaling has been implicated in a broad range of pathological processes, including cancer.

My project
Based on our comparison of gene expression in NSCs and GSCs, we wanted to further explore the role of the Wnt signaling pathway. In early 2010 I completed a screening of nine GSC primary cultures, three NSC cultures and four mixed cortex samples to investigate expression levels of Wnt ligands, receptors, inhibitors and intracellular targets.

This has revealed several interesting candidate genes that are significantly regulated between GSCs and both NSCs and normal brain, and include both surface receptors that are upregulated and pathway inhibitors that are downregulated. I have now begun to investigate the functional effects of these candidates in glioblastoma and GSCs.

Additionally I’m exploring the effects of Wnt signaling in GSCs and NSCs to get a comprehensive view of its potential role, and to further extend the comparison of these two cell types.