Obiri N I, Puri R K
Laboratory of Molecular Tumor Biology, FDA, NIH, Bethesda, MD 20852-1448.
Oncol Res. 1994;6(9):419-27.
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.
我们最近报道，多种人类实体瘤细胞表达高亲和力的白细胞介素-4受体（IL-4R）。在本研究中，我们比较了人类肾癌细胞（RCC-WS）以及淋巴细胞系RAJI（B细胞系）和H9（T细胞系）上表达的IL-4R的结构特征。在交联研究中，这三种细胞类型均表达一条主要的140 kDa的IL-4R条带。此外，一条70 kDa的条带在H9细胞中强烈表达，但在RCC-WS和RAJI细胞中仅微弱表达。当在过量白细胞介素-4（IL-4）存在的情况下进行交联研究时，未观察到这些不同种类的IL-4R，表明其具有IL-4特异性。一种多克隆抗IL-4R抗体在H9细胞中免疫沉淀出两种蛋白（140 kDa和70 kDa），而在RCC-WS肿瘤细胞和RAJI细胞中主要免疫沉淀出140 kDa的蛋白。也观察到了一条微弱的70 kDa蛋白条带。IL-4与其在RCC-WS细胞中受体的结合亲和力与在检测的H9和RAJI细胞中观察到的结合亲和力相似。然而，与T淋巴细胞相比，RCC肿瘤细胞和B淋巴细胞内化IL-4R的速度更快。尽管在所有三种细胞系中，放线菌酮对IL-4R合成的抑制作用相似，但IL-4R表达对放线菌素D抑制作用在RCC-WS和RAJI细胞上比在H9细胞上更敏感。我们的结果表明，RCC-WS肿瘤细胞上表达的IL-4R在结构上与淋巴细胞上表达的不同，因为这些细胞中IL-4R亚基的比例不同。应进行进一步研究以确定RCC和免疫细胞上表达的IL-4R蛋白的特性和功能意义。
