Enhancement of Lewis lung carcinoma cell migration by prostaglandin E2 produced by macrophages

The role of macrophages in tumor metastasis was examined by using migration of a cloned metastatic Lewis lung carcinoma (LLC) variant, LLC-C4, out of glass capillary tubes as an in vitro model for dissemination of tumor cells from a primary tumor mass. Macrophages, derived from LLC tumors of C57BL/6 mice or from peritoneal exudates of mice given injections of complete Freund's adjuvant, enhanced tumor cell migration through an indomethacin-sensitive mechanism. Resident peritoneal macrophages did not produce a tumor migration-enhancing activity but could be induced to do so by preincubation with LLC-C4 cells or their culture supernatants. The capacity of macrophages to enhance LLC-C4 migration corresponded to their secretion of prostaglandin E2. Addition of similar concentrations of prostaglandin E2 to the migration medium of LLC-C4 cells enhanced their migration out of the capillary tubes. These results suggest that macrophages, following exposure to tumor cells or their products or following stimulation with complete Freund's adjuvant, secrete elevated amounts of prostaglandin E2 which in turn may enhance tumor dissemination.