lactoferrin and Burkitt-Lymphoma

While evaluating the role of iron-binding glycoproteins on the in vitro uptake of 67Ga and 59Fe by tumor cells, it was observed that these radiometals bind to polystyrene culture tubes in the presence of transferrin or lactoferrin. The amount of 67Ga or 59Fe bound to the tube increases with glycoprotein concentrations up to 20 microgram/ml and decreases thereafter. This biphasic response is a reflection of metal-protein affinity and is greatest for 59Fe-lactoferrin. With 125I-labeled transferrin and lactoferrin, the amount of tube-bound radioactivity was inversely dependent on the glycoprotein concentration suggesting that glycoproteins bind to a limited number of binding sites on the tube wall. Approximately 10(13) glycoprotein molecules were bound per tube with an affinity constant of 1.89 X 10(7) 1/M for transferrin and 1.08 X 10(7) l/M for lactoferrin. These sites are not specific since addition of albumin inhibited the binding of radiolabeled glycoproteins to the tube. In the light of these observations, caution is required in interpreting results of cell culture experiments which have not directed attention to protein-plastic interaction.

Topics: Albumins; Binding Sites; Burkitt Lymphoma; Cells, Cultured; Gallium Radioisotopes; Humans; In Vitro Techniques; Iodine Radioisotopes; Iron Radioisotopes; Lactoferrin; Lactoglobulins; Ligands; Polystyrenes; Radioligand Assay; Radionuclide Imaging; Transferrin

In order to evaluate the mechanisms which facilitate the transfer of 67Ga from transferrin in plasma to intracellular binding sites, lactoferrin, a glycoprotein with high affinity for 67Ga, was used as a probe to study the effect of protein binding on gallium uptake by tumor cells. The in vivo effect of transferrin and lactoferrin on the biodistribution of 67Ga was studied in nude mice bearing human malignant mesothelioma. Tumor uptake of 67Ga was reduced 30% by transferrin and 57% by lactoferrin compared with 67Ga-citrate alone. Liver uptake of 67Ga, however, was significantly increased by binding to lactoferrin. The in vitro binding of 67Ga to tumor cells (Burkitt's lymphoma) was apparently promoted by the addition of transferrin or lactoferrin to the incubation medium, but this glycoprotein enhancement of gallium uptake by the cells was dependent on the albumin level, decreasing in absolute uptake as the albumin concentration was increased, suggesting nonspecific binding of glycoproteins to cells. Because of the significant amount of nonspecific binding of 67Ga-labeled glycoprotein complexes in cell culture experiments, in vitro experiments should be used with caution in developing a hypothesis on the mechanisms of cellular uptake of radiogallium. In vivo experiments suggest different mechanisms for cellular uptake of 67Ga in neoplastic tissue and in liver.

Topics: Adult; Albumins; Animals; Burkitt Lymphoma; Gallium Radioisotopes; Glycoproteins; Humans; Lactoferrin; Lactoglobulins; Male; Mesothelioma; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental; Pleural Neoplasms; Protein Binding; Transferrin

We have detected lactoferrin in tumor tissue from a patient with Hodgkin's disease and a patient with Burkitt's lymphoma. Both patients had radiogallium scans demonstrating increased uptake in the tumor tissue subsequently found to contain lactoferrin. Tissue assay for lactoferrin was performed by the indirect immunofluorescence method. Control splenic tissue showed either slight lactoferrin content or none.

Topics: Adult; Burkitt Lymphoma; Child; Fluorescent Antibody Technique; Gallium Radioisotopes; Hodgkin Disease; Humans; Lactoferrin; Lactoglobulins; Male; Radionuclide Imaging; Spleen