title: Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules.
abstract: IL-10 is a cytokine which shows various effects including inhibition of T-cell proliferation or HLA-dependent antigen presentation. In this study, we analysed the effects of exogenous or autocrine IL-10 on proliferation and expression of immunocritical surface molecules. Fourteen cultures of human melanoma cells were established from primary melanomas, locoregional lymph-node or distant metastases. In 5 melanoma cell cultures, proliferation in the presence of IL-10, anti-IL-10 antibodies (Ab) or control Ab was assessed with colorimetric and [3H]thymidine uptake assays. Flow cytometric analysis was used to quantify the expression of human leukocyte antigen (HLA) class-I, HLA class-II and intercellular adhesion molecule (ICAM)-1 and the IL-10 receptor (IL-10R). IL-10 production of melanoma cells was documented by RT-PCR and IL-10 protein was detected in the supernatants by means of ELISA. IL-10 enhanced proliferation and prolonged survival of melanoma cells in 5 out of 5 cultures. Anti-IL-10 Ab decreased proliferation. IL-10R expression was found in 12 out of 14 (86%) melanoma cell cultures. The expression of HLA-I, HLA-II and ICAM-1 on all melanoma cells that were positive for IL-10R showed a reduction of 10-60% by IL-10, whereas the surface levels of HLA-I, HLA-II and ICAM-1 in 5 out of 5 cell cultures revealed an increase of 10-170% by anti-IL-10 Ab. These findings suggest that IL-10 is an autocrine growth factor with significant impact on immunocritical molecules in melanoma. IL-10 effects have to be considered when planning therapeutic immunointerventions in melanoma patients.
authors.affiliation: Department of Dermatology, University of Zurich Medical School, Switzerland.
authors.forename: F Y
authors.initials: FY
authors.lastname: Yue
authors.forename: R
authors.initials: R
authors.lastname: Dummer
authors.forename: R
authors.initials: R
authors.lastname: Geertsen
authors.forename: G
authors.initials: G
authors.lastname: Hofbauer
authors.forename: E
authors.initials: E
authors.lastname: Laine
authors.forename: S
authors.initials: S
authors.lastname: Manolio
authors.forename: G
authors.initials: G
authors.lastname: Burg
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006133:Growth Substances / Q000494:pharmacology*; D006680:HLA Antigens / Q000096:biosynthesis*; D006681:HLA-D Antigens / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D008207:Lymphatic Metastasis / Q000473:pathology; D008545:Melanoma / Q000473:pathology* / Q000556:secondary; D009362:Neoplasm Metastasis / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D012878:Skin Neoplasms / Q000473:pathology* / Q000556:secondary; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006133:Growth Substances; D006680:HLA Antigens; D006681:HLA-D Antigens; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10