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

Clin Exp Immunol. 1994 Jan;95(1):148-55. doi: 10.1111/j.1365-2249.1994.tb06029.x.


It has previously been shown that murine sarcoma cells express high-affinity IL-4 receptors (IL-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 IL-4 on cell growth and its effect on MHC antigen expression in the presence or absence of interferon-gamma (IFN-gamma). In tissue culture, IL-4 reduced the growth of tumour cell lines and primary cell cultures studied. IL-4 had very little effect on MHC class I antigen expression on ovarian, breast and melanoma cell lines; however, MHC class II (HLA-DR) expression was enhanced on melanoma and breast carcinoma cells. IL-4 also enhanced the IFN-gamma-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-gamma may play a role in host immune response against cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • Female
  • HLA-DR Antigens / analysis
  • Histocompatibility Antigens Class I / analysis
  • Humans
  • Immunohistochemistry
  • Interleukin-4 / pharmacology
  • Melanoma / chemistry*
  • Melanoma / immunology
  • Melanoma / pathology
  • Ovarian Neoplasms / chemistry*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Receptors, Interleukin-4
  • Receptors, Mitogen / analysis*
  • Receptors, Mitogen / genetics
  • Tumor Cells, Cultured


  • HLA-DR Antigens
  • Histocompatibility Antigens Class I
  • Receptors, Interleukin-4
  • Receptors, Mitogen
  • Interleukin-4