Perineural spread of cutaneous malignancy in a live mouse and ganglion-tumour co-culture model

Gardiner, Damien (2016). Perineural spread of cutaneous malignancy in a live mouse and ganglion-tumour co-culture model MPhil Thesis, School of Medicine, The University of Queensland. doi:10.14264/uql.2016.274

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Author Gardiner, Damien
Thesis Title Perineural spread of cutaneous malignancy in a live mouse and ganglion-tumour co-culture model
School, Centre or Institute School of Medicine
Institution The University of Queensland
DOI 10.14264/uql.2016.274
Publication date 2016-05-20
Thesis type MPhil Thesis
Open Access Status DOI
Supervisor Ben Panizza
Glen Boyle
Total pages 69
Total colour pages 14
Total black and white pages 55
Language eng
Subjects 1112 Oncology and Carcinogenesis
Abstract/Summary Perineural spread (PNS) is a relatively uncommon but important method of metastatic spread in cutaneous squamous cell carcinoma (SCC) of the head and neck. PNS is defined as cancer spread along a nerve to a site distant from the main tumour bulk and should be considered distinct from perineural invasion/ infiltration (PNI), which is the microscopic finding of tumour cells infiltrating small nerves within the tumour itself. SCC is our second most common malignancy and the head and neck is the most common site to be diagnosed with an SCC. The head and neck is an important site for PNS due to the high density of both sensory and motor innervation, relatively close proximity to the central nervous system once PNS is established and large number of sensitive surrounding structures making treatment with surgery and or radiotherapy more challenging. Cutaneous SCC of the head and neck with PNS is associated with poorer outcomes in terms of local control, regional and distant metastasis and survival when compared to lesions without PNS. Little is known about the molecular mechanisms that drive this neurotrophic behaviour and much of the work to date has focused on other tumours with a predilection for PNS such as pancreatic, prostate and adenoid cystic carcinoma. In our own microarray data comparing gene expression from cutaneous SCC with PNS to cutaneous SCC with and without PNI the expression of the gene encoding transglutaminase 3 (TGM3) was significantly down regulated and the gene encoding lysyl oxidase like 2 (LOXL2) was significantly up regulated in tumours with PNS. Human cancer cell lines transfected to alter expression of these 2 genes were analysed for neurotrophic behaviour using an in vitro mouse dorsal root ganglia (DRG) co-culture assay and a new live mouse xenograft model. Results demonstrate the utility of these models as valuable tools for studying the mechanisms involved in this complex process and reinforce a potential role for LOXL2 and TGM3 in driving PNS in cutaneous SCC.
Keyword Cutaneous squamous cell carcinomas (CSCC)
Perineural invasion (PNI)
Transglutaminase 3
Lysyl oxidase like 2

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Created: Thu, 14 Apr 2016, 21:14:13 EST by Damien Gardiner on behalf of Learning and Research Services (UQ Library)