Microfluidic Devices for Studying the Effect of Netrinon-1 Neutrophil and Breast Cancer Cell Migration

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