Receptor for interleukin (IL) 13 does not interact with IL4 but receptor for IL4 interacts with IL13 on human glioma...

Recently, we have demonstrated that human (h) glioma cell lines express large number of receptors (R) for interleukin 13 (IL13) (Debinski, W., Obiri, N. I., Powers, S. K., Pastan, I., and Puri, R. K. (1995) Clin. Cancer Res. 1, 1253-1258). These cells are extremely sensitive to a chimeric protein composed of hIL13 and a derivative of Pseudomonas exotoxin (PE), PE38QQR. We have found that the cytotoxicity of hIL13-PE38QQR was blocked by hIL13 but not by hIL4 on the U-251 MG and U-373 MG cells, contrary to what was observed on several adenocarcinoma cell lines. In the present study, we further explored interactions between receptor for IL13 and IL4 on glioma cells. Established human glioma cell lines, such as DBTRG MG, Hs 683, U-87 MG, SNB-19, and A-172, are very susceptible to hIL13-PE38QQR, and the action of the chimeric toxin is not blocked by hIL4 on all these cells either. Also, hIL4 is not a competitor for 125I-hIL13 binding sites on glioma cells. Of interest, a corresponding hIL4-based chimeric toxin, hIL4-PE38QQR, is poorly active or not active on all the tested glioma cell lines. When active, however, hIL4 toxin action was blocked by hIL13. hIL13 is a competitor for 125I-hIL14 binding in a competitive binding assay on glioma cells. hIL13 and hIL4 did not affect the growth of the tested glioma cell lines. Human glioblastoma multiforme explant cells exhibited similar responses to the chimeric toxins and interleukins when compared with that found in established glioma cultures. Our results suggest that the hIL13R on glioma cells is expressed in one predominant form, the form that does not interact with IL4. Thus, this type of hIL13R is apparently different from the one demonstrated previously on several adenocarcinoma cell lines.