Model Circulating Tumor Cells Induced by Mechanical Stress

Circulating tumor cells (CTCs) display a range of specific mechanical properties that set them apart from tumor-residing cells. CTCs face a series of mechanobiology-related challenges: they need to break from the tumor, intravasate, withstand fluid shear stress (FSS) in circulation and then attach to the vessel wall for extravasation. Established carcinoma cell lines are adherent and grow on the surface of cell culture dishes. Such cells may represent tumor residents or advanced colonization of the metastatic niche; however, they are not adequate models of CTCs. Here, we describe the generation of "model CTCs" by subjecting carcinoma cell lines to circulation-imitating FSS in a microfluidic system. Such cells can be characterized by analytical methods of choice, including atomic force microscopy (AFM) based nanomechanical phenotyping. Indeed, model CTCs display nanomechanical properties resembling patient-isolated CTCs and are well suited for studies on mechanotransduction.