Abstract
Ovarian cancer is the most lethal gynecological cancer with a five-year survival rate as low as 30%. Early diagnosis could offer high chances of survival as most ovarian cancer cases are diagnosed only after metastasis has taken place. Some of the challenges in diagnosis and treatment are due to ovarian cancer's preference for the transcoelomic metastatic pathway over the more well-known hematogenic pathway, where spheroids suspended in the peritoneal cavity invade through the mesothelial layer that lines it. Spheroids for in vitro experiments have been generated for decades using common methods such as hanging drops and liquid overlay, but these models typically do not account for the fluid shear stress present in vivo, especially following the formation of ascites. One method to mimic this in vitro is to use dynamic cell culture to generate shear stress. Fluid movement parameters (rotation, shaking, etc.) can be tuned to achieve physiologically-relevant shear stress while facilitating the formation of spheroids. Dynamic culture improves the roundness and size consistency of spheroids, facilitating functional assays such as spheroid migration and mesothelial clearance. The addition of shear stress is expected to increase the metastatic behavior of spheroids as it better recreates the in vivo environment. This model also provides a platform for incorporating other in vivo elements such as co-culture, use of ascites samples, etc. This work is ultimately aimed at improving our fundamental understanding of peritoneal metastasis with new insights for determining optimal therapeutic approaches.
Citation Format: Timothy J. Masiello, L.P. Madhubhani Hemachandra, and James Castracane. USING A DYNAMIC, LOW-SHEAR ENVIRONMENT TO MIMIC PHYSIOLOGICAL FLUID SHEAR STRESS IN OVARIAN CANCER IN VITRO MODELING [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr TMIM-078.
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