Open AccessExpression of high‐affinity IL‐4 receptors on human melanoma, ovarian and breast carcinoma cells
Author(s) -
OBIRI N. I.,
SIEGEL J. P.,
VARRICCHIO F.,
PURI R. K.
Publication year - 1994
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1994.tb06029.x
Subject(s) - ovarian carcinoma , biology , cancer research , melanoma , cell culture , northern blot , immunohistochemistry , receptor , breast carcinoma , pathology , microbiology and biotechnology , ovarian cancer , immunology , cancer , gene expression , medicine , breast cancer , gene , biochemistry , genetics
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 (K d ) 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.