title: Synthesis of platelet-activating factor (PAF) in transformed cell lines of a different origin.
abstract: Interest in the possible involvement of the platelet-activating factor (PAF) in tumor growth and invasiveness has been stimulated by the recognition that PAF influences various biological responses relevant to metastatic diffusion, such as angiogenesis, adhesiveness to endothelia and cellular motility. In the present study, we investigated the extent to which PAF is synthesized by a series of human and murine transformed cell lines of a different histotype. Synthesis of PAF was studied by combining the 14C-acetate incorporation into PAF with the quantitative analysis of PAF performed by a procedure based on gas chromatography-mass spectrometry with a negative ion chemical ionization. In the presence of the Ca2+ ionophore A23187, cultures of human melanoma (Hs294T), fibrosarcoma (HT1080) and colon carcinoma (LS180) cell lines synthesized conspicuous amounts of PAF, comparable to those produced by resident peritoneal macrophages. Substantial quantities of PAF were also synthesized by the murine melanoma (F10-M3 cells). PAF synthesis was rather limited in RSV-transformed Balb/c3T3 (B77-3T3) cells and in one of their high metastatic variants (B77-AA6 cells), although it was more abundant in the latter. We also investigated whether certain cytokines, such as TNFalpha and IFNgamma might induce PAF synthesis in our systems of cell lines which we found to express mRNAs encoding receptors for these cytokines. We observed that PAF synthesis was enhanced in human melanoma and colon carcinoma cell lines and in the murine B77-AA6 cells to levels comparable to those obtained with the Ca2+ ionophore. Synthesis of PAF was not inducible by TNFalpha in murine F10-M3 melanoma cells. IFNgamma also stimulated PAF synthesis in human and murine melanoma lines, and in human LS180 colon carcinoma line, but not in the B77-AA6 cells. PAF synthesis was also inducible by exogenous PAF in the human and murine melanoma lines, and in the human LS180 colon carcinoma line, all of which expressed cell surface PAF receptors. PAF synthesis was not inducible by exogenous PAF in the B77-AA6 cells, which do not express PAF receptors.
authors.affiliation: Department of Experimental Pathology and Oncology, University of Florence, Italy. fallania@unifi.it
authors.forename: Anna
authors.initials: A
authors.lastname: Fallani
authors.forename: Barbara
authors.initials: B
authors.lastname: Grieco
authors.forename: Emanuela
authors.initials: E
authors.lastname: Barletta
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mugnai
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giorgi
authors.forename: Laura
authors.initials: L
authors.lastname: Salvini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ruggieri
mesh_terms: D016475:3T3 Cells; D019342:Acetic Acid / Q000378:metabolism; D000818:Animals; D002461:Cell Line, Transformed; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D043562:Receptors, G-Protein-Coupled; D017471:Receptors, Interferon / Q000032:analysis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000096743:Interferon gamma Receptor
chemical_list: D019342:Acetic Acid; D007371:Interferon-gamma; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; C039351:platelet activating factor receptor