Characterization and mutual ligand-induced modulation of epidermal growth factor and interferon-alpha receptors on renal carcinoma cells in vitro.
We have determined the binding of epidermal growth factor (EGF) and interferon (IFN)-alpha to their specific receptors on four renal carcinoma cell lines. CaKi-2, a-498 and ACHN cell lines express high numbers, and CaKi-1 expresses low number of EGF receptors (EGFRs). On all four renal carcinoma cell lines, we have also detected specific IFN-alpha binding sites. EGF and IFN-alpha binding to their receptors caused modulation of the other ligand's receptor binding. Scatchard analyses of binding data showed that IFN-alpha treatment leads to an increase of EGFR number in three out of four cell lines and to a decrease of EGFR number in one out of four (CaKi-1). No significant changes in EGF binding affinities were detected. EGF induced a reduction in IFN-alpha receptor number in all four cell lines without significant changes in IFN-alpha binding affinities. We hypothesize that presence of EGF in the microenvironment of renal cancer cells may modulate the biological effects of IFN and consequently decrease its antiproliferative activity.
Heise
H
H
Division of Hematology and Oncology, Klinikum rechts, Isar der Technischen Universität München, Germany.
Depenbrock
H
H
Rastetter
J W
JW
Hanauske
A R
AR
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001667:Binding, Competitive; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D066246:ErbB Receptors