Ex Vivo Microfluidic Model Identifies a Role for Shear Stress during Ovarian Tumor Cell Attachment to Peritoneal Mesothelial Cells
Abstract
Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. We show that the attachment of ovarian tumor cells to mesothelium is impacted by fluid shear stresses in a dynamic manner. We find that ovarian tumor cells secrete factor(s) that enhance the ability of ovarian tumor cells to more efficiently attach, and remain attached, to the mesothelium in the presence of fluid shear stress. This work advances the study of ovarian tumor cell metastasis, describing a robust method to screen and identify therapeutically targetable pathways of ovarian tumor cell-mesothelial cell intercommunication to potentially mitigate ovarian cancer progression.
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