SUMMARYThe pregnancy-associated substance early pregnancy factor (EPF) has previously been reported as a product of tumours of germ cell origin. More recently EPF (or an EPF-related substance, tEPF) has aiso been detected in the serum of patients bearing tumours of non-germ cell origin. We report here the production oftEPF by a variety of cultured transformed and tumour eell lines, of both germ and non-germ celt origin. Antibodies specific for EPF remove all tEPF activity from tumottr cell conditioned medium. tEPF production is found to be associated with cell division; tEPF is no longer detected after growth arrest or differentiation. Co-eulUire of tumour eells with increasing doses of anti-EPF monoclonal antibodies resulted in a significant, dose-dependent decrease in rate of cell growth and viability. Similar anti-EPF concentrations had no effect on the concanavalin A induced proliferation of mouse spleen cells. These studies suggest, therefore, that tEPF is a growth-regulated product of cultured tumour and transformed ceils. These celts are also dependent upon tEPF for continued growth, i.e. tEPF is acting in the autocrine mode.

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Incubation of primary nerve cell cultures and of crude synaptosomal preparations with neuraminidase released sialic acid from both gangliosides and sialoglycoproteins. After this treatment, the pattern of ganglioside distribution was severely modified with a decrease of polysialogangliosides (GD1b, GT1b, Gt1L, GQ1) and a dramatic increase in monosialoganglioside GM1. The choline influx into neuraminidase treated cells and organelles was reduced by 30--50% but the efflux was unmodified. In particular the high affinity mechanism of choline uptake disappeared and the low affinity mechanism was modified in both cases. The disappearance of the high affinity uptake mechanism was not followed by a decreased acetylcholine synthesis as it should be if the current theories on choline uptake and acetylcholine synthesis are correct. Our present data thus confirm our previous hypothesis that choline metabolism regulates choline uptake rather than the other way round as is suggested by the theories most widely accepted at present. Choline uptake was unaffected by pretreatment of cells and organelles with tetanus toxin suggesting that the effect of neuraminidase on the choline uptake were either mediated through glycoproteins or through gangliosides other than those which bind to tetanus toxin (GD1b and GT1b). Several speculative models for explaining the effect of neuraminidase on choline uptake are proposed.