Glioblastoma Multiforme (GBM) is a highly aggressive primary brain tumour with almost complete patient mortality attributing to its invasive nature and destruction of surrounding brain tissue. Despite progression of numerous drug clinical trials for GBM treatment, few objective responses are observed and the median survival of 15 months has increased little over the past decade. Our understanding of key molecular mechanisms to GBM tumour progression, however, has exploded during this time but we still fail to make significant clinical progress. In recent years focus has shifted from the receptor tyrosine kinase family, once thought to be the primary drivers of malignancy, towards multifunctional signalling molecules. These molecules have provided understanding into the complex and cross-signalling pathways that has shed new light on an old mystery. The heterogeneous GBM tumour is not easily controlled by a single pathway and the burden of resistance and recurrence has proven to be the reply of multiple signalling molecules that act along similar or completely independent pathways to achieve the same function.
We aimed to expand on the current knowledge of tumour progression and signalling through the investigation of a single controversial protein IGFBP3. Our findings established an important function for IGFBP3 in GBM pathogenesis. IGFBP3 was found to be upregulated along with other well characterised oncogenes. In vitro investigation demonstrated a role for IGFBP3 in regulating cell viability, migration and invasion. Interestingly while IGFBP3 presented as an oncogene in LN18 and LN229 cells, in U87MG cells it suppressed migration and MMP2 secretion, while still maintaining a pro-oncogenic role in cell viability and invadopodia analysis. We also identified IGFBP3 as a mediator of temozolomide and radiotherapy resistance. These results suggest IGFBP3 is a potent multifunctional protein with a key role in GBM pathogenesis and may be of use for clinical prognosis.