Morphological analysis of tumor cell/endothelial cell interactions under shear flow

Area of Science:

• Biophysics
• Cell Biology
• Cancer Research

Background:

• Hematogenous cancer metastasis involves tumor cells (TCs) entering, surviving, and extravasating through the endothelium.
• Understanding TC extravasation mechanisms, particularly under flow-induced mechanical stress, is crucial but poorly understood.
• Previous studies often overlooked the role of shear stress in TC-endothelial cell interactions during extravasation.

Purpose of the Study:

• To investigate tumor cell-endothelial cell interactions and extravasation under dynamic flow conditions.
• To differentiate and quantify tumor cell spreading patterns on endothelial monolayers.
• To elucidate the influence of shear stress on tumor cell spreading and extravasation.

Main Methods:

• Utilized a parallel-plate flow chamber to simulate blood circulation conditions.
• Co-cultured endothelial cell (EC) monolayers as an endothelial barrier model.
• Introduced tumor cells (TCs) under defined flow fields and observed cell behavior using live microscopy.

Main Results:

• Identified two distinct TC spreading patterns: radial spreading (associated with extravasation) and axial spreading (forming a TC-EC mosaic monolayer).
• Developed a quantitative method to compare spreading modes based on area and aspect ratio changes.
• Observed that axial spreading extent increased with elevated shear stress, unlike radial spreading.

Conclusions:

• Flow-induced shear stress significantly influences tumor cell spreading mechanisms on endothelial barriers.
• Axial spreading, distinct from extravasation, is promoted by shear stress.
• Quantitative analysis of spreading patterns provides a basis for understanding extravasation dynamics under physiological flow conditions.