Eosinophils in a tri-cell multicellular tumor spheroid (MTS)/endothelium complex

Eosinophils have been found in infiltrates of many different cancers. It is still unclear as to whether they are passive bystanders in the cellular milieu or active cellular agents in host responses. Thus their harmful or helpful nature remains equivocal. We have developed an in vitro tri-cell model of eosinophils, MCF-7 breast tumor cell spheroids and HUVEC endothelial cells to examine the binding and association of eosinophils with both the tumor and the endothelia and the ensuing action of the tumor. Eosinophils bound very rapidly to the tumor spheroid and remained tightly bound throughout the 24 hr culture period. Histological staining of the tri-cell complex revealed highly granulated eosinophils as well as large amounts of degranulated protein diffused throughout the spheroid. IL-5 treatment of eosinophil: MTS complexes resulted in destruction of the tumor cells, particularly those which had grown out from the spheroid onto the endothelial cells. Eosinophils, pretreated with IL-5 before interaction with the tumor or endothelial cells, bound aggressively to the endothelial cells, thereby preventing tumor attachment. This eosinophil tri-cell tumor model system mimics clinical observations with regards to binding to epithelial and endothelial cells, dispersal of granular proteins throughout the tumor and also tumor destruction. Because it closely mirrors in vivo cellular interactions, it allows one to study more closely the mechanism(s) of eosinophil killing, the modulation of eosinophil activity and the testing of therapeutic interventions. The accommodation of the model to tumor invasion, using metastatic tumor cells and extracellular matrices such as matrigel, will help to elucidate a role for eosinophils (and their mediators) in cancer invasion and metastasis.