Protruding Geometry Provides Potential Homing Sites of Circulating Tumor Cells

Abstract

Circulating tumor cells (CTCs) must adhere to the vascular endothelium to initiate metastasis, yet the role of vessel wall topography remains unclear. We present an integrated microfluidic platform combining defined protruding geometries, live cell imaging, and controlled perfusion to study CTC homing. Using a multiscale device that reproduces hierarchical vascular branching, we show that CTCs accumulate preferentially at locations with protruded geometry, including bifurcations, sharp corners and positively curved segments. At these hotspots, a viscoelastic, polymer-like network assembles, capturing CTCs and accompanying progressive multicellular aggregation. This network undergoes stretching and elastic recoil even under laminar flow. Mechanistically, knockdown of DSG2 and ITGB3 reduces retention, suggesting a potential anti metastasis strategy targeting molecular mechanical coupling. Computational fluid dynamics simulations indicate that hotspots coincide with pronounced velocity and pressure perturbations. Our experiments identify local geometry as a critical determinant of CTC arrest and provide a platform for studying the physical mechanisms of metastatic homing.