Eosinophil Cell Lines in a Tri-Cell Multicellular Tumor Spheroid (MTS)/Endothelium Complex: Down Regulation of Adhesion and Integrin Molecules- Implications of Metastasis Inhibition

摘要

Eosinophils are nonimmune inflammatory cells which are intricately involved in helminthic infections and allergic hypersensitivity reactions (1, 2). Activated eosinophils produce a host of mediators, including cytokines which can be both detrimental as well as helpful to the host (3, 4, 5). Cytokines such as IL-lalpha, IL-1beta and TNFalpha, also produced by eosinophils, upregulate adhesion molecule expression on both endothelial and tumor cells (6, 7). Increased expression of adhesion molecules such as ICAM-1, V-CAMl and E-Selectin (ELAM-l) on tumor cells is correlated with increased invasiveness and metastasis (8, 9, 10). Multicellular tumor spheroids are three- dimensional cell culture systems which have been shown to model the growth characteristics of tumors as well as their metastatic potential(11, 12, 13). In light of this, tumor spheroids have more recently been used as a model for examining tumor-endothelial cell interactions in order to better understand the interactions of the tumor with its microvascular environment. We have utilized the tumor spheroid model system to study not only its interaction with endothelial cells, but also examine the effector role of eosinophils in tumor:endothelial cell interaction. We have shown that peripheral blood eosinophils from allergic and asthmatic individuals can inhibit the growth of both breast and prostate tumor cells (14, 15). In this study we attempted to examine the hypothesis that eosinophils infiltrate breast spheroids (14) release of their contents into the tumor microenvironment and that these eosinophil mediators, to include cytokines, can modulate spheroid adherence and invasion. In order to do this we attempted to set up an eosinophil tumor spheroid:endothelial tri-cell complex (16).