Binding of epidermal growth factor-dextran conjugates to cultured glioma cells.

Abstract

Some gliomas, melanomas and squamous carcinomas have large numbers of EGF receptors which could, in these cases, be used for targeting with toxic agents. We investigated whether EGF could be conjugated to dextran, which is a suitable carrier for toxic agents, without losing its ability to bind to the receptor. Dextran of 20 kDa molecular weight was activated with I-cyano-4-dimethylamino pyridinium tetrafluoroborate (CDAP) yielding highly active pyridinium-isourea derivatives. EGF was coupled to the activated dextran through the amino terminus and glycine was added to block residual activity. The EGF-dextran conjugate was, after purification on Sephadex G25 and Sephacryl 200 columns, tested for its receptor binding properties on human malignant glioma, U343MGaC12:6, cells. The conjugate inhibited binding of 125I-EGF in a competitive assay, showing that the binding was receptor-specific. Dextran conjugated with glycine, without EGF, had no inhibitory effect. The conjugate was radio-labelled either on the EGF part with 125I or on the dextran part with 3H-glycine, and the internalization patterns were compared to the internalization of 125I-EGF. The radioactivity of the conjugates remained cell-associated for more than 20 hr, regardless of whether the radioactivity was on the EGF or on the dextran part, while the radioactivity of unconjugated EGF rapidly disappeared from the cells. Most of the cell-associated radioactivity was, at all analysed time intervals, located intracellularly. Thus, it seems promising to use dextran, conjugated with EGF, as a carrier of, for example, toxic radioactive nuclides.

• Authors: A Andersson, A Holmberg, J Carlsson, J Carlsson, J Pontén, B Westermark
• Journal: International journal of cancer (Int J Cancer) Vol. 47 Issue 3 Pg. 439-44 (Feb 01 1991) ISSN: 0020-7136 [Print] United States
• PMID: 1704355 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dextrans
• Iodine Radioisotopes
• Nitriles
• Pyridinium Compounds
• epidermal growth factor-dextran conjugate
• Tritium
• 1-cyano-4-dimethylaminopyridinium
• Epidermal Growth Factor
• ErbB Receptors

Topics

• Dextrans (metabolism)
• Epidermal Growth Factor (metabolism)
• ErbB Receptors (metabolism)
• Glioma (metabolism, pathology, ultrastructure)
• Humans
• Iodine Radioisotopes
• Kinetics
• Nitriles (metabolism)
• Protein Binding
• Pyridinium Compounds (metabolism)
• Temperature
• Time Factors
• Tritium
• Tumor Cells, Cultured