Microfluidic Devices for Studying the Effect of Netrin‐1 on Neutrophil and Breast Cancer Cell Migration

Abstract

Netrin‐1 is well‐known for its chemoattractive and chemorepulsive properties for axon guidance. Early studies report that netrin‐1 inhibits granulocyte migration. On the other hand, netrin‐1 can promote cancer cell migration and invasion. The underlying mechanisms are not well understood, which requires more in‐depth characterizations of netrin‐1 mediated immune and cancer cell migration. The present study, for the first time, employs microfluidic devices that are recently developed to quantitatively investigate the effects of netrin‐1 on the motility and chemotaxis of human blood neutrophils and human breast cancer cells under well‐controlled gradient conditions. The results show that netrin‐1 reduces chemokinetic motility of human neutrophils, which is accompanied with reduced cell polarization and spreading. In addition, netrin‐1 reduces neutrophil chemotaxis to N‐formyl‐Met‐Leu‐Phe on fibronectin substrate but interestingly not on collagen substrate. By contrast, netrin‐1 promotes the migration of human breast cancer cells. Furthermore, it is found that netrin‐1 reduces neutrophil chemotaxis to the supernatant of human breast cancer cell culture. Collectively, this microfluidic cell migration study provides quantitative characterizations of the effects of netrin‐1 on the motility and chemotaxis of neutrophils and breast cancer cells, and further suggests the potential role of netrin‐1 in regulating neutrophil recruitment to breast cancer microenvironments.

A Novel Microfluidic Device for the Neutrophil Functional Phenotype Analysis: Effects of Glucose and Its Derivatives AGEs

“…The basic design of the F4-chip was referred to the published microfluidic devices from our and some other groups [ 31 , 34 , 39 ]. In this study, the F4 chip was equipped with four independent units ( Figure 1 A–C), which were very important for the cell migration experiments.…”

Recent advances in microfluidics-based cell migration research

“…Indeed, many researchers have now focused on the crosstalk between immune cell and cancer cell during metastasis. [104][105][106][107][108] The immunotherapy proposes a new therapeutic strategy for treating cancer patients. With the rapid developing technology, microfluidic organ-on-chip devices have the potential to provide a comprehensive explanation of the complex mechanisms behind cell transmigration in the future.…”