Prostaglandin E2 production by EL 4 leukemia cells from C57BL/6 mice: mechanism for tumor dissemination.

Murine EL 4 leukemia cells contained and secreted prostaglandin E2 (PGE2). PGE2 was secreted into the culture media during in vitro growth, as well as into plasma during growth in the peritoneum of inbred C57BL/6 mice. For the study of the role of PGE2 in tumor dissemination, migration of EL 4 cells out of glass capillary tubes was used as an in vitro model for tumor spread in a host. PGE2 enhanced the in vitro migration of EL 4 cells while indomethacin, a prostaglandin synthesis inhibitor, reduced the extent of migration. When EL 4 cells were allowed to migrate into medium containing both indomethacin and PGE2, the cells exhibited an enhanced migration ability suggesting an extrinsic effect on cells by PGE2. The participation of tumor-derived PGE2 in promoting tumor spread in a host was supported by demonstration that EL 4 cells grown in indomethacin-treated mice secreted less PGE2 and had reduced in vivo dissemination ability. These results indicated that tumor spread was promoted by tumor-derived PGE2. The extent of migration and dissemination can be reduced by prostaglandin synthesis inhibitors such as indomethacin.