The roles of hypoxia on neuroblastoma cell migration and invasion

Rice, Michael
The roles of hypoxia on neuroblastoma cell migration and invasion. Master of Philosophy thesis, University of Liverpool.

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Solid tumours are predisposed to hypoxic conditions due to cellular proliferation outpacing the rate of angiogenesis. Hypoxia is associated with enhanced tumour aggression. We aimed to study how hypoxia influences the migration and invasion of Neuroblastoma, a common and highly lethal, enigmatic childhood cancer. Fluorescently labelled Neuroblastoma cell lines were cultivated under atmospheric (‘normoxic’) or hypoxic conditions for 3 days before implantation upon the chorioallantoic membrane (CAM) of chick embryos and observed in-vivo for tumour formation and metastasis. Tumourigenesis was successful regardless of oxygen levels. Normoxic cells failed to metastasise, conversely hypoxic cells invaded the embryo forming tumour spheres in several organs. Interestingly, ‘normoxic’ cell invasion was observed when implanted alongside hypoxic cells resulting in co-invasion and independent microtumour deposition. These processes were later identified as ‘HIF dependent,’ following pretreatment of cells with DMOG. In conclusion we found an increase in metastatic phenotype following exposure to hypoxia via stabilisation of the HIF transcription factor. This CAM model was also utilised in order to begin to understand the molecular mechanisms underpinning the aggressive and erratic clinical behaviour of Neuroblastoma.

Item Type: Thesis (Master of Philosophy)
Additional Information: Date: 2013-08 (completed)
Subjects: ?? RJ ??
Divisions: Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 01 Aug 2014 11:10
Last Modified: 16 Dec 2022 04:40
DOI: 10.17638/00013757