The role of invadopodia in glioma invasion and response to therapeutics
Malignant gliomas caused approximately 2.3% of cancer-related deaths in the USA with over 22,000 new patients expected annually. The most prevalent form of glioma and the tumour with the worst prognosis is the glioblastoma multiforme (GBM,WHO grade IV). The prognosis for patients with GBM tumours remains poor with a median survival of only 14.6 months, after receiving the current standard treatment consisting of surgery, radiotherapy and temozolomide. The characteristic of all gliomas is their extensive infiltration, which thwarts efforts to completely remove or ablate these malignant cells.
A property shared by several types of tumour cells is an ability to form structures known as invadopodia. These are dynamic actin-dependent, membrane protrusions which proteolytically degrade extracellular matrix (ECM) substrates via the activities of numerous proteases. We have observed invadopodia in glioma cell lines and primary tumour cells derived from ex vivo cultured GBM specimens, suggesting a role for invadopodia in glioma invasion.
Invadopodia formation and function are dependent on multiple proteins and signaling pathways. Therefore understanding how invadopodia are regulated and controlled within a tumour cell is essential and strategies aimed at disrupting invadopodia could form the basis of novel anti-invasive therapies for treating glioma patients in the future. This project will involve studies that explore the role of a number of invadopodia proteins in glioma cells, how they contribute to their invasive phenotype and ultimately influence their response to treatment.
Potential Skills/Techniques: Cell Biology techniques including cell culture and cell transfections (overexpression and siRNA gene silencing), western blotting, zymography, immunofluorescence and immunohistochemistry, confocal microscopy, migration/invasion assays, reporter assays, ultracentrifugation, proteomics, RNA Seq, datamining
Dr Stanley Stylli, Project Leader,
Clarissa Whitehead, PhD student
Marija Dinevska, Honours Student
Natalia Gazibegovic, Masters Student
Dr Andrew Morokoff (University of Melbourne, Australia)
Dr Rodney Luwor (University of Melbourne, Australia)
Dr Hong-Jian Zhu (University of Melbourne, Australia)
Associate Professor Fred Hollande (University of Melbourne, Australia)
Dr Christina Molck (University of Melbourne, Australia)
Mr Cameron Nowell (Monash University, Australia)
Friends of The Royal Melbourne Hospital Neuroscience Foundation
Royal Melbourne Hospital Lottery Grant-in-Aid
For a complete listing of Dr Stanley Stylli's publications on Research Gate
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