Abstract
We report that cytosine arabinoside (Ara-C), a cytosine analogue that at low doses causes phenotypical changes on human leukemia cells in vitro and in vivo, induces growth inhibition of oropharyngeal cancer KB and lung adenocarcinoma A549 cell lines. An increase in the number of epidermal growth factor and transferrin receptors (EGFR, TrfR) is induced by Ara-C on these cells. Maximal EGFR up-regulation occurs 96 h after the beginning of Ara-C exposure while maximal TrfR up-regulation is detected 24 h later. These effects occur without changes in the affinity of EGFR and TrfR for their ligands. Two classes of EGF-binding sites with aK d of 0.055 nM and 2.3 nM respectively, and one class of transferrin-binding sites with aK d of about 4 nM are detected on both untreated and Ara-C-treated KB cells. [3H]Thymidine uptake is clearly stimulated on KB cells by nanomolar concentrations of EGF and transferrin, whereas in Ara-C-treated cells [3H]thymidine uptake is not increased by EGF and transferrin under conditions where maximal EGFR and TrfR up-regulation occurs. The enhanced EGF and transferrin binding is paralleled by a twofold increase of in vitro targeting of Ara-C-treated KB and A549 cells with anti-EGFR 108.1 mAb and anti-TrfR OKT9 mAb. We propose that Ara-C could provide a new approach for the improvement of the therapeutic index of anti-EGFR and anti-TrfR immunoconjugates.
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This work has been supported by the Italian Association for Cancer Research (A.I.R.C.) and by the National Council of Research (C.N.R.) of Italy, contract 92.02274.PF39
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Caraglia, M., Tagliaferri, P., Correale, P. et al. Cytosine arabinoside increases the binding of125I-labelled epidermal growth factor and125I-transferrin and enhances the in vitro targeting of human tumour cells with anti-(growth factor receptor) mAb. Cancer Immunol Immunother 37, 150–156 (1993). https://doi.org/10.1007/BF01525428
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DOI: https://doi.org/10.1007/BF01525428