Growth factors for human tumor clonogenic cells elaborated by macrophages isolated from human malignant effusions

Abstract

We previously demonstrated that macrophages isolated from human malignant effusions support colony formation of autologous tumor cells in soft agar. We now demonstrate that macrophages (derived from effusions of patients with ovarian, breast, colon, or lung adenocarcinomas) secrete a soluble factor(s) that enhances the ability of a human epithelial tumor cell line (SW-13) to clone in soft agar. Macrophages increased colony growth 5 to 10-fold in a concentration dependent manner, although inhibition of cell growth was observed in the presence of high concentrations of macrophages. We attempted to increase production of tumor colony stimulating factor by exposing macrophages to lipopolysaccharide, concanavalin A, or phytohemagglutinin. Exposure of macrophages to these agents failed to increase their ability to secrete stimulatory factors. Macrophages were cultured for 1 day to 6 weeks in the presence of GCT-CM, a source of granulocyte-macrophage colony stimulating factor and the ability of these cultured macrophages to support colony growth assessed. The ability of macrophages to support colony growth declined gradually with time in culture reaching 50% of control values at 14 days, but remained at this level until 5 weeks of culture. The results of this study indicate the SW-13 cells may provide a quantitative assay for studying monocyte-derived tumor colony stimulating factors.