Optical coherence tomography imaging of ovarian cancer invasion
Item statusRestricted Access
Embargo end date31/07/2022
Hallas-Potts, Amelia May
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.