The role of invadopodia in glioma invasion and response to therapeutics

Project Details

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

Researchers

Dr Stanley Stylli, Project Leader,

Clarissa Whitehead, PhD student

Marija Dinevska, Honours Student

Natalia Gazibegovic, Masters Student

Collaborators

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)

Funding

Friends of The Royal Melbourne Hospital Neuroscience Foundation
Royal Melbourne Hospital Lottery Grant-in-Aid

Research Outcomes

https://www.findanexpert.unimelb.edu.au/display/person56485#tab-publications

Research Publications

For a complete listing of Dr Stanley Stylli's publications on Research Gate
https://www.researchgate.net/profile/Stanley_Stylli/publications

Research Group

Brain Tumour Biology and Therapies



Faculty Research Themes

Cancer

School Research Themes

Cancer in Medicine



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Surgery

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