Abstract A047: Modeling the role of the fallopian tube in the prevention and spread of high grade serous cancer using a multi-organ platform

Abstract

Abstract It is now recognized that a large percentage of high grade serous ovarian cancers arise in the fallopian tube and colonize the ovary as the primary metastatic step. One of the risk factors associated with ovarian cancer is the lifetime number of ovulations. Few models are currently available that allow the process of ovulation and the development of ovarian cancer to be studied. To address this gap, our team developed a microphysiological platform called PREDICT-multi-organ-system (MOS). PREDICT-MOS contains 30 wells for culturing organs and 60 pumps with precisely controlled flow rates. Human fallopian tube tissue can be grown in an air-liquid interface, while murine ovaries can be engineered to ovulate while producing and secreting physiological concentrations of hormones and proteins over the entire process of ovulation. Importantly, these secreted factors are contained in the device within the media and can therefore precisely model local concentration gradients and temporal exposure of the human fallopian tube tissues. First, we uncovered that the ovary secretes versican during the cycle to enhance ovarian migration, adhesion, and expansion within the ovarian microenvironment. We revealed that fallopian tube tumor cells stimulate the ovary to produce testosterone, which enhanced fallopian tube invasion and stem cell marker expression. Next, we profiled the expression of secreted extracellular vesicles that are produced by the fallopian tube on the platform. Extracellular vesicles may provide a new form of liquid biopsy, but understanding the cargo expressed from normal cells is critical for understanding the importance of cancer EV’s during progression. Finally, we have engineered the platform to allow for real-time invasion using an insert technology and a modified pump that allows for interaction between the organs. Overall, the integration of organ-on-chip technology with key human tissues allows for the in-depth analysis of the role of ovulation in the onset and spread of high-grade serous cancer from the fallopian tube. Citation Format: Joanna Burdette. Modeling the role of the fallopian tube in the prevention and spread of high grade serous cancer using a multi-organ platform [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A047.