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© 1993 Oxford University Press

research-article

Platelet activating factor, an endogenous mediator of inflammation, induces phenotypic transformation of rat embryo cells

S.A.L. Bennett, L.C.C. Leite 1 and H.C. Birnboim 2

Department of Biochemistry, University of Ottawa and Ottawa Regional Cancer Centre 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6

2To whom reprint requests should be sent

The ability of platelet activating factor (PAF), a potent endogenous inflammatory agent, to induce phenotypic transformation of primary rat embryo cells (RECs) was investigated. RECs are composed predominantly of fibroblasts, with some epithelial cells and a few neuronal and muscle cells. A 1 h period of treatment with PAF (1 × 10–8–1 × 10–6 M) increased the ability of RECs to (i) form foci, (ii) reach a high saturation density in complete medium, (iii) grow in low serum-containing medium and (iv) exhibit anchorage-independent (AI) growth. Similar changes were achieved with C-PAF (1 × 10–10–1 × 10–8 M), an active, non-metabolizable analog of PAF, but not by lyso-PAF (1 × 10–10–1 × 10–6 M), a biologically inactive metabolite of PAF. All of the PAF-induced phenotypic changes could be inhibited by pretreatment with a PAF receptor antagonist, CV3988 (1 × 10–6 M). Pretreatment of RECs with genestein (1 µg/ml) also completely inhibited all four measures of PAF-induced REC transformation indicating that tyrosine kinase activity may be required for the observed changes in phenotype. Pretreatment with indomethacin (2 × 10–7 M) blocked the PAF-induced increases in focus formation and saturation density without affecting PAF-induced alterations in growth in low serum or AI growth. This indicates that PAF may exert some of its effects through a cyclooxygenase product. Pretreatment with staurosporine (5 × 10–8 M) failed to alter any of the PAF-induced effects, suggesting that protein kinase C activity is not involved in REC transformation by PAF. Our results provide the first evidence that PAF, released by activated phagocytes in and around areas of inflammation, may contribute to the process of malignant transformation.


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