title: E-series prostaglandins are potent growth inhibitors for some B lymphomas.
abstract: The ability of prostaglandins (PG) to inhibit the growth of B cell lymphomas was investigated. Macrophage-secreted PGE2 was previously shown to promote unresponsiveness to antigen in normal B lymphocytes. This observation suggested that B lymphomas might also be regulated by prostanoids. Five non-PG-secreting Ly-1+ B lymphomas (CH12, CH31, CH33, NBL and WEHI-231) were incubated for 24-72 h with PGE2, PGE1 or PGF2 alpha. The level of lymphoma growth at the end of culture was determined using a colorimetric assay which detects only viable cells. A marked heterogeneity was observed with respect to the sensitivity of these lymphomas to PGE2 and PGE1. CH31 was very sensitive, being growth inhibited by as little as 10(-8) M PGE. In contrast, CH12, a more mature lymphoma, was highly resistant, whereas CH33, NBL and WEHI-231 were of intermediate resistance. All five lymphomas demonstrated little or no growth inhibition when cultured with PGF2 alpha. Moreover, unlike PGE2, PGF2 alpha failed to elevate intracellular cAMP levels. It was previously shown that CH31, CH33 and WEHI-231 could be growth inhibited by anti-immunoglobulin antibodies which cross-link surface immunoglobulin. Interestingly, these three lymphomas were rendered more sensitive to this treatment if PGE2 was present. For example, 10(-8) M PGE2 alone had little effect on CH33, but significantly augmented growth inhibition induced by suboptimal quantities of anti-immunoglobulin antibody. Cholera toxin, another agent which was found to rapidly elevate intracellular cAMP levels, also synergized with suboptimal doses of anti-immunoglobulin to induce growth inhibition. Overall these data suggest that, in vivo, macrophage-secreted prostanoids may slow the growth of some lymphomas and that anti-immunoglobulin or anti-idiotype treatment may be more effective in the presence of agents which elevate cAMP such as E-series PG.
authors.affiliation: Immunology Unit of the Cancer Center, University of Rochester, NY.
authors.forename: R P
authors.initials: RP
authors.lastname: Phipps
authors.forename: D
authors.initials: D
authors.lastname: Lee
authors.forename: V
authors.initials: V
authors.lastname: Schad
authors.forename: G L
authors.initials: GL
authors.lastname: Warner
mesh_terms: D000818:Animals; D001402:B-Lymphocytes; D002455:Cell Division / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D006131:Growth Inhibitors; D066298:In Vitro Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D051379:Mice; D011458:Prostaglandins E / Q000494:pharmacology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D006131:Growth Inhibitors; D011458:Prostaglandins E; D011947:Receptors, Antigen, B-Cell; D002772:Cholera Toxin; D015237:Dinoprost; D000242:Cyclic AMP