Cell fusion has been used to study some of the factors involved in the process of metastasis. Highly metastatic rat mammary adenocarcinoma cells were fused with various non-metastatic cells and the hybrid clones isolated. These were then tested for their metastatic potential either by injecting the cells intravenously and measuring lung colony formation or by injecting the cells subcutaneously and measuring their ability to form lymphatic metastases. With most hybrid clones tested, the metastatic potential was either inhibited or greatly suppressed; thus this phenotype is a recessive characteristic. We also monitored the hybrid cells' ability to produce plasminogen activator (PA) a serine proteinase thought to be involved in the formation of metastatic lung foci. Whilst the highly metastatic parent cells produced large quantities of PA, none could be detected in the non-metastatic lines. Although the hybrid clones produced little PA activity this could not be correlated with their decreased metastatic potential in that one clone, after extensive in vitro culture, reverted to a more metastatic line without a concomitant increase in PA activity. The suppressed PA activity may be due to the presence of an inhibitor that is spontaneously produced by the hybrid cells.

Summary. The formation of lung colonies after i.v. injection of highly metastatic rat mammary adenocarcinoma cells (MAT 13762) was greatly reduced by concurrent treatment of rats with heparin. The procoagulant activity (PCA) of these cells, and of a non-metastatic adenocarcinoma (DMBA-8) has therefore been measured. These have been compared with PCA expressed by MAT 13762 cell derivatives including a non-metastatic hybrid clone (MAT 13762 X DMBA-8), its metastatic revertant, and clones selected in vivo from lung metastases. Potent PCA was expressed on intact MAT 13762 cells and in their spent culture media, the latter being sedimentable and associated with shed membrane vesicles. Cell-derived PCA, unlike thromboplastin, was equally effective in factor Vll-deficient and normal bovine plasma. There were, however, no major differences in the expression of PCA (either cell-associated or shed) between the metastatic and non-metastatic cell types studied. Plasminogen activator (PA) production by these cells has also been measured. The results arc discussed in the context of the possible role of fibrin formation and fibrinolysis in the metastatic process.

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Summary. The cflect of the iron-chelating agent desferrioxamine on lymphocyte proliferation has been studied. Desferrioxamine at concentrations of 15 ^M totally inhibited the proliferation of Concanavalin A-stimuIaled lymphocytes, whereas iron-saturrited dcsferrio.xamine was ineffective. Other metal salts, however, had little or no effect on the inhibition induced by this drug. Desferrioxamine was more effective at suppressing proliferation of T lymphocytes than B lymphocytes and additionally suppressed mi.xed lymphocyte cultures and the generation of cytotoxit T cells.