Examining the impact of fluid shear stress on cancer-fighting immune cells
Cancer cells begin inside a localized tumor but can metastasize and spread throughout the body. Individual cancer cells can break off from the tumor and enter the bloodstream in a process known as hematogenous dissemination. But the vascular microenvironment is a dangerous place for cancer cells, as they are hunted by immune cells known as natural killer (NK) cells while simultaneously contending with high fluid shear stress.
Each hazard individually threatens cancer cells, but a synergistic effect increases cell deaths when both NK cells and fluid shear stress are present. Hu et al. investigated the mechanisms leading to increased NK cell effectiveness in the presence of fluid shear stress.
The team employed a microfluidic system to subject their cancer cell samples to a wide range of shear flows and monitored how effective the NK cells were in each case. By performing a PCR test on the samples, they identified the relationship between fluid shear stress and the boost in NK cell effectiveness.
“Fluid shear stress during hematogenous dissemination can activate NK cells and then promote the killing effect towards circulating tumor cells,” said author Youhua Tan. “The underlying mechanism is that NK cells can perceive mechanical forces via surface protein NKG2D, which then facilitates the delivery of the enzyme granzyme B into the tumor cells.”
The authors plan to expand on these results in two key directions.
“Based on these findings, our next steps are to utilize patient samples to show the clinical relevance of our study and to investigate the survival mechanism of the surviving tumor cells under both fluid shear stress and NK cells,” said Tan.
Source: “Fluid shear stress enhances natural killer cell’s cytotoxicity towards circulating tumor cells through NKG2D-mediated mechanosensing,” by Bing Hu, Ying Xin, Guanshuo Hu, Keming Li, and Youhua Tan, APL Bioengineering (2023). The article can be accessed at https://doi.org/10.1063/5.0156628 .