Abstract 2725: Long-term live imaging of ovarian cancer invasion using optical coherence tomography

Abstract

Abstract Ovarian cancer is a lethal gynecological disease but the histological subtypes of ovarian cancer differ in their biology and clinical behavior. We have previously demonstrated that ovarian carcinoma cell line behavior is related to the primary tumor origin, providing a rationale for in vitro modelling to identify differences between ovarian tumor types. To better understand the in vivo behavior of ovarian tumors we are developing a patient-specific ex vivo model that can be used to investigate individual patient tumor behavior, alongside a microscopy tool that allows live imaging to investigate tumor invasion and eventually response to therapy over time. Optical coherence tomography (OCT) is a non-damaging imaging technique used clinically to investigate ocular disease in vivo. Real time live imaging of ovarian cancer cell lines over 5 days was established on a commercial OCT system using non-serous ovarian cancer cell lines TOV21G and A2780 seeded onto a collagen/fibroblast matrix. We have previously used histology to reveal that TOV21G cells invade into collagen with a spindle-like morphology characteristic of sarcomatous tumor cell invasion whereas A2780 invade in clusters characteristic of epithelial tumor cells. Using live OCT imaging we have visualized how these different invasive patterns develop over time. Live imaging facilitates investigation of different invasive behaviors with greater granularity, resolving differences in phenotypic behavior. We are now developing machine learning algorithms that can quantitatively analyze the speed, depth and frequency of invasion over time. High-grade serous (HGS) carcinomas commonly spread transcoelomically along peritoneal surfaces, seeding secondary tumors on and in the peritoneum and omentum. We have demonstrated that HGS cell lines do not invade into common in vitro extracellular matrix substitutes such as matrigel and collagen, highlighting the need for a biological technique that better recapitulates the in vivo behavior. We have developed ex vivo cultures using patient-derived tumor and matched normal omentum to better mimic in vivo invasive behavior. We have used both tissue slices and mechanically dissociated tumor cells cultured with patient omentum compared with in vitro derived collagen/fibroblast matrices, demonstrating retention of tumor viability over a 10 day period. We are now using the OCT technique to live image and quantitatively analyze patient tumor-omentum interactions over time, comparing those data with histology to determine the interaction with invasion substrate at fixed time points over the 10 day culture period. OCT is a promising and novel tool for the investigation of tumor invasion ex vivo. Applying this to ovarian cancer patient-derived matched tumor and omentum provides the opportunity to assess not only invasive capacity but also patient-specific response to therapy. Citation Format: Amelia Hallas-Potts, Jonathan H. Mason, Jessica H. Lim, Michael Churchman, Pierre Bagnaninchi, Charlie Gourley, C. Simon Herrington. Long-term live imaging of ovarian cancer invasion using optical coherence tomography [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2725.