Binding, internalization and degradation of EGF-dextran conjugates in two human bladder-cancer cell lines.
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.
Sjöström
A
A
Biomedical Radiation Sciences, Uppsala University, Sweden. Anna.Sjostrom@bms.uu.se
Bue
P
P
Malmström
P U
PU
Nilsson
S
S
Carlsson
J
J
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*
D003911:Dextrans; D004338:Drug Combinations; D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors