Expression of high-affinity IL-4 receptors on human melanoma, ovarian and breast carcinoma cells.
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.
Obiri
N I
NI
Division of Cellular and Gene Therapies, FDA, Bethesda, MD 20892.
Siegel
J P
JP
Varricchio
F
F
Puri
R K
RK
D001943:Breast Neoplasms / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000494:pharmacology; D008545:Melanoma / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000032:analysis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4