Expression of high-affinity IL-4 receptors on human melanoma, ovarian and breast carcinoma cells

Abstract

SUMMARY It has previously been shown that murine sarcoma cells express high‐affinity IL‐4 receptors (1L‐4R) which are internalized after binding to the ligand (Puri et al., Cancer Res 1991; 51:3011‐7). We have also reported that human renal cell carcinoma cells express high‐affinity IL‐4R. and IL‐4 inhibits tumour growth in vitro (Obiri et al, J Clin Invest 1993; 91:88). In this study we investigated the expression and function of IL‐4R on other human solid tumours. Human melanoma, ovarian carcinoma and breast carcinoma cell lines were assessed for the cell surface expression of IL‐4R by radio‐ligand receptor binding and for IL‐4R gene expression by Northern blot analysis. Primary cultures of mesothelioma and neurofibrosarcoma cells were similarly investigated. Human melanoma, ovarian carcinoma and breast carcinoma cell lines expressed IL‐4R on their cell surface with a dissociation constant (Kd) of 140‐549 pM. These tumour lines expressed a single 4 kb species of mRNA for IL‐4R. Similarly, primary cultures of mesothelioma and neurofibrosarcoma cells were positive for the IL‐4R mRNA by Northern blot analysis. Fresh, non‐cultured mesothelioma and neurofibrosarcoma tumour sections were also positive for the presence of IL‐4R as determined by immunohistochemistry of frozen sections using anti‐IL‐4R antibody. In order to study possible functions of IL‐4R, we evaluated the effects of 11.‐4 on cell growth and its effect on MHC antigen expression in the presence or absence of interferon‐gamma (IFN‐γ)‐ In tissue culture, IL‐4 reduced the growth of tumour cell lines and primary cell cultures studied. IL‐4 had very title effect on MHC class I antigen expression on ovarian, breast and melanoma cell lines; however. MHC class I (HLA‐DR) expression was enhanced on melanoma and breast carcinoma cells. IL‐4 also enhanced the IFN‐γ‐induced class II expression on melanoma and breast carcinoma cells. Taken together, our observations indicate that IL‐4R are expressed on a variety of human solid tumours and these receptors may be functional. IL‐4 alone and in combination with IFN‐γ may play a role in host immune response against cancers.

Targeting Interleukin-4 Receptor α with Hybrid Peptide for Effective Cancer Therapy

“…High-affinity interleukin-4 receptor (IL-4R) is highly expressed on the surface of various human solid tumors including renal cell carcinoma, melanoma, breast carcinoma, ovarian carcinoma, glioblastoma, AIDS-related Kaposi's sarcoma, and head and neck squamous cell carcinoma (14)(15)(16)(17)(18)(19)(20). IL-4R-targeted protein-based immunotoxin was being tested in the clinic for the treatment of human solid tumors (3,21,22).…”

Endogenous Interleukin-4 Promotes Tumor Development by Increasing Tumor Cell Resistance to Apoptosis

“…Besides the increased IL-4 expression in cancer patients, the elevated amount of IL-4 receptor (IL-4R) has also been detected on various tumor cells using I 125 -IL-4 binding assay or flow cytometry, including renal cell carcinoma (10), malignant melanoma (11), glioblastoma (12), head and neck cancer (13), etc., which usually express 1,000 to 13,000 IL-4R molecules per cell with variations depending on the tumor types, whereas much lower number of IL-4R, ranging about <50 to 500 molecules per cell, is present in such normal cells as B cells (14), endothelial cells (15), and monocytes (16). Moreover, the binding affinity of IL-4R on tumor cells is increased compared with those on normal cells (17).…”

Associations Between Three Polymorphisms in the Interleukin-4 Receptor Gene and Risk of Cancer: a Meta-analysis

“…& , Yu-Qiao Zhou & , Xiao-Xu Li, Xin Jin, Li-Li Wang, Lei Lei, Yu Zhou, Jiang Lu, Xin Zeng, Hong-Xia Dan*, Ga Liao*, Qian-Ming Chen high level of IL-4R expression has been observed on the surface of ovarian and breast carcinoma cells (Obiri et al, 1993(Obiri et al, , 1994. Moreover, IL-4 level was higher in higher-stage tumor tissues compare with tissues from lower-stage patient (Onishi et al, 1999).…”