High Shear Stresses under Exercise Condition Destroy Circulating Tumor Cells in a Microfluidic System

Area of Science:

• Biomedical Engineering
• Oncology
• Cardiovascular Physiology

Background:

• Circulating tumor cells (CTCs) are crucial for cancer metastasis.
• The impact of exercise-induced shear stress on CTCs remains largely unexplored.

Purpose of the Study:

• To investigate the effects of exercise-relevant shear stress on CTCs.
• To determine the viability and death mechanisms of CTCs under varying hemodynamic conditions.

Main Methods:

• A microfluidic circulatory system was developed to simulate exercise-induced shear stresses.
• Breast, ovarian, lung, and leukemic cancer cells were exposed to low (15 dynes/cm²) and high (60 dynes/cm²) shear stress.
• Cell viability, necrosis, and apoptosis were assessed post-exposure and during incubation.

Main Results:

• High shear stress (60 dynes/cm²) significantly reduced CTC viability compared to low shear stress (15 dynes/cm²).
• High shear stress induced necrosis in over 90% of CTCs within 4 hours, followed by apoptosis in survivors.
• Highly metastatic and drug-resistant breast cancer cells showed reduced viability under prolonged high shear stress.

Conclusions:

• Intensive exercise-induced high shear stress can effectively destroy CTCs.
• Exercise may represent a viable strategy to prevent cancer metastasis by targeting CTCs.
• Leukemic cells exhibited greater resistance to shear stress compared to solid tumor-derived CTCs.