Activated eosinophils infiltrate MCF-7 breast multicellular tumor spheroids

Background: Previous studies in our laboratory have shown that activated eosinophils and eosinophilic cell lines inhibit the in vitro growth of MCF-7 breast tumor cells. We have also shown that IL-4 and IL-5 partially inhibit MCF-7 growth in vitro. In this study MCF-7 multicellular tumor spheroids (MTS) were developed to study the effect of eosinophils and IL-4 on tumor growth. Materials and Methods: Hypo- and hyperdense metrizamide density gradient fractions of eosinophils from peripheral blood of individuals with mild to moderate esoinophilia were co-cultured with 2-day-old MCF-7 MTS in medium containing bacto agar overlay at 37degreesC. Results: Light microscopic analyses revealed the attachment of eosinophil effector cells to the spheroid borders. Moreover, the culture media was greater than 90% devoid of effector cells. At six days post co-culture, very large spheroids were observed in both test and control dishes; however the necrotic cores in the co-cultures were more intense and larger than in the control. When MCF-7 tumor cells (1 x 10(6)) were pretreated with IL-4 at 0.5 ng/ml, there was a dramatic decrease in the number of spheroids formed. Conclusion: These data strongly indicate that cytokines like IL-4 and perhaps other eosinophil mediators are capable of killing and inhibiting tumor growth; they suggest that tumor infiltrating eosinophils can degranulate and release toxic inhibitory factors into the tumor milieu which destroy the surrounding tumor. These observations, along with the use of the eosinophil: MTS tumor model provide a unique model system for in depth studies of the role of eosinophils and the cytokines they produce in breast cancer and may offer potential therapeutic implications.