Macrophage-neoplastic cell interactions: implications for neoplastic cell growth.

Abstract

Subcutaneous transplantation of EL4 lymphoma cells within C57BL10 mice evoked an oedematous inflammatory response involving increased leukopoiesis within the bone marrow, a blood leukocytosis, an influx of leukocytes into the transplants and surrounding host connective tissues, and extensive remodelling of surrounding host connective tissues involving fibroplasia and angiogenesis. Dexamethasone not only significantly reduced the numbers of circulating blood leukocytes within C57BL10 mice bearing the subcutaneous EL4 lymphoma transplants, but also reduced the oedematous inflammatory response to the transplants. The decreased influx of inflammatory leukocytes into the site of EL4 lymphoma cell transplantation within the dexamethasone-treated mice, was accompanied by reduced growth of the transplants. Although the EL4 lymphoma cells produce factors with Colony Stimulating Factor activity and with chemotactic activity for cells of the monocyte-macrophage lineage, they do not appear to produce fibroblast growth factors directly but can induce (or stimulate) macrophages to generate fibroblast growth factors in vitro. While not directly inhibiting the growth of subcutaneous fibroblasts in vitro, dexamethasone does suppress the production and/or activity of fibroblast growth factors generated through macrophage-EL4 cell interactions in vitro. The inhibitory effects of dexamethasone on macrophage influx, fibroplasia and angiogenesis within the connective tissue surrounding the EL4 lymphoma transplants appear to be casually related events and would account for the inhibitory effect of dexamethasone on the growth of the lymphoma transplants.