title: Binding, internalization and degradation of EGF-dextran conjugates in two human bladder-cancer cell lines.
abstract: Bladder carcinomas often have an increased number of epidermal growth factor (EGF) receptors. The EGF receptors can, in these cases, be targets for toxic conjugates. In this study, EGF-dextran conjugates were used as targeting agents with therapeutic potential. The binding, internalization and degradation of 125I-EGF-dextran conjugates in J82 and RT4, 2 different bladder cancer cell lines, were investigated. The behaviour of 125I-EGF was studied as a comparison. The 125I-EGF-dextran showed a continuous increase in binding up to 24 hr, while 125I-EGF exhibited maximum binding after about 90 min. Both cell lines showed similar binding patterns. The binding of 125I-EGF-dextran and 125I-EGF was, on both cell lines, receptor-specific since the binding could be displaced with non-radioactive EGF. Analysis of internalized and membrane-bound 125I activity after administration of 125I-EGF-dextran showed that most of the activity was membrane-bound. A large part of both the internalized and the membrane-bound activity remained cell-associated up to 24 hr. The internalized and membrane-bound activity after administration of 125I-EGF decreased rapidly and only a small fraction remained cell-associated after 24 hr. 125I-EGF-dextran remained cell-associated, with only a limited release of low- and high-molecular-weight radioactivity throughout the 24-hr period, while 125I-EGF was extensively degraded and released into the incubation medium as low-molecular-weight radioactivity during this time. Several qualities of the 125I-EGF-dextran conjugates might be favourable for targeted radiotherapy.
authors.affiliation: Biomedical Radiation Sciences, Uppsala University, Sweden. Anna.Sjostrom@bms.uu.se
authors.forename: A
authors.initials: A
authors.lastname: Sjöström
authors.forename: P
authors.initials: P
authors.lastname: Bue
authors.forename: P U
authors.initials: PU
authors.lastname: Malmström
authors.forename: S
authors.initials: S
authors.lastname: Nilsson
authors.forename: J
authors.initials: J
authors.lastname: Carlsson
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism*; D004338:Drug Combinations; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000378:metabolism*; D008970:Molecular Weight; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D003911:Dextrans; D004338:Drug Combinations; D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors