Effects of hemodynamic shear stress on circulating tumor cells

• Main Author: How, Yunhan
• Other Authors: Kathy Qian Luo
• Format: Final Year Project
• Language: English
• Published: 2014
• Subjects: DRNTU::Engineering::Bioengineering
• Online Access: http://hdl.handle.net/10356/60808
• Institution: Nanyang Technological University

Metastasis has been observed to be an inefficient process, but a consensus has not been reached as to which steps of metastasis are potentially rate-limiting. The effects of sustained exposure to hemodynamic shear stress on the viability and behaviour of circulating tumor cells (CTCs) are also not fully understood. In this study, a pulsatile microfluidic system was developed to mimic the physiological flow profile in the blood vessel. MDA-231-C3 was circulated and recovered repeatedly to obtain a series of flow-selected breast cancer cell lines (231-S1 to 231-S6). The effect of fluid shear stress on CTC survival was studied by quantifying the cell viability and level of apoptosis at 0-hr, 12-hr and 24-hr time points of circulation. It was observed that a large portion of CTCs becomes fragmented under sustained exposure to shear stress, and <5-10% of the cells undergo apoptosis during circulation. Therefore necrosis, instead of apoptosis, is likely to be the more dominant mechanism by which CTCs die. Flow-selected cells were shown to acquire enhanced survival ability in a shear flow microenvironment. They also exhibit elongated cell morphology, greater drug resistance and higher expression of MnSOD, as compared to normal 231-C3.