Cancer invasion and metastasis

Lab head: Dr Guy Lyons
Location: Dermatology Research Labs, Rm W350 Blackburn Bldg

The key characteristic that defines a tumour as being malignant is its ability to spread locally (invade) and to distant sites (metastasise). Our group is studying the molecular, genetic and cellular mechanisms of how cancers progress from a normal tissue to a malignant tumour. We are particularly interested in squamous cell carcinomas of the skin, mouth and throat. The roles of oncogenic papilloma viruses and processes such as epithelial-mesenchymal transitions are being studied using innovative cell and animal models. Translation of these findings to improving treatments, particularly radiation therapy, is being undertaken. We are also investigating novel mechanisms by which cells evolve within tumours, using fluorescent cell and animal systems, as well as computer simulation. 

Website: http://sydney.edu.au/medicine/people/academics/profiles/glyons.php
Lab members: Dr Angela Hong, Dr Mei Zheng, Mr Paul Sou, Ms Naomi Delic, Mr Askar Abubakar, Ms Deanna Jones
Funding: Cancer Council NSW, Cancer Australia, Lifehouse
Research approach equipment: This program encompasses a range of molecular and cell biological methods, including: • cell culture models • plasmid and virus vector construction • quantitative gene expression analysis • biochemical and immunological characterisation of proteins • microscopy • flow cytometry • small animal models
Publications:

Pang E, Delic NC, Hong A, Zhang M, Rose BR and Lyons JG (2010) "Radiosensitization of oropharyngeal squamous cell carcinoma cells by human papillomavirus 16 oncoprotein E6*I" Int. J. Rad. Onc. Biol. Phys. Accepted for publication 2nd July, 2010. doi:10.1016/j.ijrobp.2010.06.028

Hong A, Dobbins T, Lee CS, Jones D, Jackson E, Clark J, Armstrong B, Harnett G, Milross C, O'Brien C and Rose B (2010) "Relationships between epidermal growth factor receptor expression and human papillomavirus status as markers of prognosis in oropharyngeal cancer." Eur. J. Cancer 46, 2088-2096

Hong AM, Dobbins TA, Lee CS, Jones D, Fei J, Clark JR, Armstrong BK, Harnett GB, Milross CG, Tran N et al. (2010) "Use of cyclin D1 in conjunction with human papillomavirus status to predict outcome in oropharyngeal cancer." Int. J. Cancer, 

Hong AM, Grulich AE, Jones D, Lee CS, Garland SM, Dobbins TA, Clark JR, Harnett GB, Milross CG, O'Brien CJ and Rose BR (2010) "Squamous cell carcinoma of the oropharynx in Australian males induced by human papillomavirus vaccine targets." Vaccine 28, 3269-3272

Moloney FJ, Lyons JG, Bock VL, Huang XX, Bugeja M and Halliday GM (2009) "Hotspot mutation of BRM in non-melanoma skin cancer." J. Invest. Dermatol. 129, 1012-1015

Fei J, Hong A, Dobbins TA, Jones D, Lee CS, Loo C, Al-Ghamdi M, Harnett GB, Clark J, O'Brien CJ and Rose B (2009) "Prognostic significance of vascular endothelial growth factor in squamous cell carcinomas of the tonsil in relation to human papillomavirus status and epidermal growth factor receptor." Ann. Surg. Oncol. 16, 2908-2917

Halliday GM and Lyons JG (2008) "Inflammatory doses of UV may not be necessary for skin carcinogenesis." Photochem. Photobiol. 84, 272-283

Lyons JG, Lobo E, Martorana AM and Myerscough MR (2008) "Clonal diversity in carcinomas: its implications for tumour progression and the contribution made to it by epithelial-mesenchymal transitions." Clin. Exp. Metastasis 25, 665-677

Lyons JG, Patel V, Roue N, Fok SY, Soon L, Halliday GM and Gutkind JS (2008) "Snail up-regulates proinflammatory mediators and inhibits differentiation in oral keratinocytes." Cancer Res. 68, 4525-4530

Failes TW, Cullinane C, Diakos CI, Yamamoto N, Lyons JG and Hambley TW (2007) "Studies of a cobalt(III) complex of the MMP inhibitor marimastat: a potential hypoxia-activated prodrug." Chemistry 13, 2974-2982

Cell-cell interactions in tumour progression

Primary supervisor: Guy Lyons

Cancer is a disease in which cells acquire mutations in key genes that change their behaviour. Under pressures of limiting space and nutrients, cells that have an advantage in survival and proliferation are selected and dominate the tissue. This mutation and selection process is, in fact, an example of evolution. The clonal cooperation (or interclonal cooperativity) hypothesis of tumour progression predicts that genetically distinct clones of tumour cells interact in order for the tumour as a whole to progess to malignancy. These interactions allow the tumour cells to invade tissues locally and spread to draining lymph nodes and other organs. This project will test the clonal cooperation hypothesis in an established in vivo experimental model of human squamous cell carcinoma (SCC). Candidate oncogenes will be introduced independently into non-tumorigenic SCC cells, using plasmid and viral vectors. Emphasis will be placed on oncogenes that increase the motility or proliferation of cells. Lines expressing individual oncogenes will be tested for their ability to display several malignant behaviours, both on their own and when mixed with other oncogene-expressing lines, to determine whether clonal cooperation occurs. Cell culture experiments aimed at determining whether clonal cooperation contributes to proliferation and invasion of the extracellular matrix will also be undertaken, and in vivo tumour formation will also be tested. The methods encountered to undertake this project will include recombinant DNA technology, mammalian cell culture, live-cell microscopy, 3-dimensional fluorescent microscopy and bioimaging of living mice. 

Discipline: Pathology
Co-supervisors: Vani Raviraj, Cathy Payne, Gary Halliday
Keywords: Cancer, Genetic processes, Genetic processes
Contact: Email Guy Lyons