Ovarian cancer is the most lethal gynaecological disease in the developed world. The term
ovarian cancer describes a heterogeneous group of tumours that grow in the ovary but are
not necessarily of ovarian origin. There are several histotypes of ovarian tumours which show
distinct cellular origin, molecular aberrations and disease progression in patients; however,
this heterogeneity is not reflected in the treatments currently available.
Epithelial ovarian
cancer (also termed ovarian carcinoma) accounts for 90% of all ovarian cancer diagnoses; it
encompasses all cancers that arise from the epithelium and involve the ovary. Ovarian
carcinomas commonly spread along peritoneal surfaces, particularly the omentum, and
invade superficially into tissues. This body of work shows the development of novel
techniques to characterise the invasive behaviour of epithelial ovarian tumours.
Firstly, cell lines and ascites were used to characterise the behaviour of epithelial ovarian
tumours and identify differences between serous and non-serous ovarian carcinomas.
Recent genomic analysis has shown that many of the most commonly used ovarian cancer
cell lines have been mischaracterised, leading to erroneous conclusions and a gap in the
translation of laboratory research into novel treatments for patients. The behaviour of 5
serous and 5 non-serous ovarian cancer cell lines was characterised using 2D migration, cell
cycle parameters and 3D invasion behaviour into different substrates.
This work shows that
ovarian cancer cell lines derived from non-serous carcinomas migrate and invade more
aggressively than those derived from high-grade serous carcinomas.
These differences may
reflect differences in the behaviour of the primary tumour types from which the cell lines
were derived.
Next, an imaging tool that allows long-term time-lapse imaging to investigate tumour
invasion was developed. Optical coherence tomography (OCT) is a non-damaging imaging technique used clinically to investigate ocular disease in vivo. In this body of work, time-lapse
imaging of ovarian cancer cell lines over 5 days was developed on a commercial OCT system.
The establishment of time-lapse OCT imaging made it possible to visualise how different
invasive patterns developed over time. Application of the optimised time-lapse imaging
protocol to the study of cell lines facilitated the investigation of different invasive behaviours
in more detail, resolving differences in phenotypic behaviour over time.
Finally, to better understand the in vivo behaviour of ovarian tumours, a patient-specific ex
vivo model was developed to investigate individual patient tumour behaviour. Explant
cultures using patient-derived tumour and matched normal omentum were developed to
better mimic in vivo invasive behaviour and imaged using OCT. Tissue slices and mechanically
dissociated tumour cells were cultured with patient omentum and compared with in vitro
derived collagen/fibroblast matrices, demonstrating retention of tumour viability over a 14
day period.
Together these data show the development of novel techniques to characterise the invasive
behaviours of epithelial ovarian tumours. This work provides evidence that time-lapse OCT is
a promising and novel tool for the characterisation of tumour invasion in vitro. Applying this
to ovarian cancer patient-derived matched tumour and omentum ex vivo provides the
opportunity to assess patient-specific invasive behaviour. The optimisation and development
of techniques described here can provide future opportunities to develop preclinical models
to further our understanding and clinical management of ovarian tumours
