Characterization of interleukin-4 receptors expressed on human renal cell carcinoma cells.
We have recently reported that a variety of solid human tumor cells express high-affinity interleukin-4 receptors (IL-4R). In this study, we have compared structural characteristics of IL-4R expressed on human renal cell carcinoma cells (RCC-WS) and the lymphoid cell lines RAJI (B-cell line) and H9 (T-cell line). In crosslinking studies, the three cell types expressed a predominant 140 kDa IL-4R band. In addition, a 70 kDa band was expressed strongly in H9 cells but only faintly on RCC-WS and RAJI cells. These different species of IL-4R were not observed when crosslinking studies were performed in the presence of excess interleukin-4 (IL-4), indicating IL-4 specificity. A polyclonal anti-IL-4R antibody immunoprecipitated the two species (140 and 70 kDa) in H9 and predominantly the 140 kDa species in RCC-WS tumor cells and RAJI cells. A faint band for the 70 kDa protein was also observed. The affinity of IL-4 binding to its receptor in RCC-WS cells was similar to the binding affinity observed in H9 and RAJI cells examined. However, the RCC tumor cells and B lymphoid cells internalized IL-4R more rapidly compared to T lymphoid cells. Although IL-4R synthesis was similarly inhibited by cycloheximide in all three cell lines, IL-4R expression was more sensitive to actinomycin D inhibition on the RCC-WS and RAJI cells than on H9 cells. Our results suggest that IL-4R expressed on RCC-WS tumor cells are structurally different from those expressed on lymphoid cells because the proportions of IL-4R subunits differ in these cells. Further studies should be performed to determine the identity and functional significance of IL-4R proteins expressed on RCC and immune cells.
Obiri
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NI
Laboratory of Molecular Tumor Biology, FDA, NIH, Bethesda, MD 20852-1448.
Puri
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RK
D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure*; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000378:metabolism / Q000648:ultrastructure; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000473:pathology; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D007457:Iodine Radioisotopes; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D003609:Dactinomycin; D015847:Interleukin-4; D003513:Cycloheximide