MACROPHAGES AND MULTICELLULAR TUMOR SPHEROIDS IN COCULTURE - A 3-DIMENSIONAL MODEL TO STUDY TUMOR-HOST INTERACTIONS - EVIDENCE FOR MACROPHAGE-MEDIATED TUMOR-CELL PROLIFERATION AND MIGRATION

In a new co-culture model involving multicellular tumor spheroids and different phenotypes of human macrophages, we studied the effects of t he latter on migration and proliferation of the human colon carcinoma cell line, HRT-18. The macrophage phenotypes are detectable with monoc lonal antibodies and are inducible in culture. 12-O-tetradecanoyl-phor bol-13-acetate-activated macrophages are associated with the phenotype 27E10, which is ax acute inflammatory macrophage. The glucocorticoid- induced macrophage phenotype RM3/1 is associated with the down-regulat ion of inflammation. The phenotype resembling the mature resident macr ophage termed 25F9 arises spontaneously in prolonged culture. It could be shown that inflammatory macrophages are localized at invasive area s of the tumor-host interface of colorectal carcinoma, whereas residen t and anti-inflammatory macrophages were found in the central tumor re gion or at well-bordered areas of the tumor-host interface. The result s obtained with this co-culture model show that 27E10-associated macro phages stimulate tumor cell migration and inhibit tumor cell prolifera tion. RM3/1 bad only a slight inhibiting effect on proliferation and a slight promoting effect on migration. The 25F9-positive macrophage-st imulated tumor cell proliferation and inhibited migration completely. This investigation indicates that this in vitro system is useful for s tudying different macrophage effects on tumor cells and that indeed pr oliferation and migration of tumor cells could be influenced ix an opp osite manner by different types of macrophages.