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.
Dr Stanley Stylli, Project Leader,
Clarissa Whitehead, PhD student
Dylan Jones, Honours 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
1: Expression of the adaptor protein Tks5 in human cancer: prognostic potential.
Stylli SS, Luwor RB, Kaye AH, I ST, Hovens CM, Lock P. Oncol Rep. 2014
Sep;32(3):989-1002. doi: 10.3892/or.2014.3310. Epub 2014 Jul 4. PubMed PMID:
2: Prognostic significance of Tks5 expression in gliomas. Stylli SS, I ST, Kaye AH, Lock P. J Clin Neurosci. 2012 Mar;19(3):436-42. doi: 10.1016/j.jocn.2011.11.013. Epub 2012 Jan 16. PubMed PMID: 22249020.
3: Nck adaptor proteins link Tks5 to invadopodia actin regulation and ECM degradation. Stylli SS, Stacey TT, Verhagen AM, Xu SS, Pass I, Courtneidge SA, Lock P. J Cell Sci. 2009 Aug 1;122(Pt 15):2727-40. doi: 10.1242/jcs.046680. Epub 2009 Jul 13. PubMed PMID: 19596797; PubMed Central PMCID: PMC2909319.
4: Invadopodia: at the cutting edge of tumour invasion. Stylli SS, Kaye AH, Lock P. J Clin Neurosci. 2008 Jul;15(7):725-37. doi: 10.1016/j.jocn.2008.03.003. Epub 2008 May 12. Review. PubMed PMID: 18468901.
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