The dynamic morphology of the transferrin-transferrin receptor system in human leukaemia/lymphoma cell lines and its relation to iron metabolism and cell proliferation.

Some functional and morphological aspects of the transferrin-transferrin-receptor (Tf-TfR) system were investigated in 12 human haematopoietic tumour cell lines. The iron uptake ability, studied by 59Fe labelling, varied considerably between individual tumour cell lines. The studies of the morphology of the Tf-TfR system by fluorescence based methods using labelling by FITC-Tf, and by indirect immunofluorescence (OKT9 anti-TfR monoclonal antibody) demonstrated that the iron uptake was the result of receptor-mediated endocytosis (RME) of the Tf-TfR complex. The RME was better developed in the haemoglobin synthesizing K-562 cells than in the monocytic U-937 cells, suggesting that the intracellular iron processing capacity differs from cell type to cell type. The efficiency of iron-uptake, transport and storage was related to cell growth. Inhibition of growth by increasing cell densities or by drug treatments (phorbol ester TPA and difluoromethylornithine DFMO) was thus accompanied by a decrease in surface Tf binding, in cellular Tf handling capacity and in iron accumulation. TPA induced a redistribution of the TfR-pool to the intracellular space as demonstrated by morphology.