Journal of Experimental Medicine, Vol 164, 1259-1273, Copyright © 1986 by Rockefeller University Press
Immune regulation of the L5178Y murine tumor-dormant state. I. In vivo and in vitro effects of prostaglandin E2 and indomethacin on tumor cell growth
CM Liu, T Okayasu, P Goldman, Y Suzuki, K Suzuki and EF Wheelock
Immunization and intraperitoneal challenge of DBA/2 mice with L5178Y
lymphoma cells results in the suppression and maintenance of the L5178Y
cells in a tumor-dormant state in the peritoneal cavity for many months.
Cell-mediated immune responses involving lymphocytes and macrophages are
involved in maintenance of the tumor-dormant state. Macrophages that have
increased immunosuppressive activity and that produce increased amounts of
PGE2 appear in the peritoneal cavity of tumor-dormant mice before the
breakdown of the tumor-dormant state and formation of ascitic tumors. We
report here that the tumor-dormant state can be terminated with formation
of ascitic tumors by treatment of tumor-dormant mice with PGE2. Treatment
with indomethacin results in inhibition of tumor cell growth and
elimination of all recoverable tumor cells. Cultures of peritoneal cells
(PC) from mice harboring L5178Y cells in a tumor-dormant state were used to
analyze the PGE2 and indomethacin effects. Tumor cells did not grow out in
the high-cell density PC cultures prepared from many tumor-dormant mice,
but addition of PGE2 to these cultures resulted in tumor cell growth. The
tumor cell growth that did occur in the PC cultures from some tumor-dormant
mice was associated with PGE2 production by the associated host cells, and
the addition of indomethacin to these cultures inhibited both PGE2
synthesis and tumor cell growth. Removal of plastic-adherent cells from the
PC cultures eliminated the restraint on tumor cell growth. These
experiments suggest that L5178Y tumor cells are maintained in a tumor-
dormant state by host peritoneal cells, which are under PGE2 regulation.
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