title: Expression of interleukin 2 receptors on human carcinoma cell lines and tumor growth inhibition by interleukin 2.
abstract: We have previously shown that human squamous cell carcinomas (SCC) express the interleukin 2 receptor (IL2R)-alpha and -beta chains, and that the ligand, IL2, directly inhibits growth of the tumor in vitro and in vivo in the tumor xenograft-nude mice model. We now show that the alpha and beta chains of IL2R are expressed on a variety of human carcinoma cell lines and on normal human keratinocytes in early-stage cultures. While all carcinoma cells in a population expressed IL2R-alpha and -beta proteins, in keratinocytes obtained from different normal donors, variable proportions of cells were positive, as measured by flow cytometry. The carcinoma lines and 2/5 keratinocyte lines studied were also found to contain transcripts for the IL2R-gamma chain detectable by combined reverse transcription-PCR (RT-PCR) and hybridization with the specific cDNA probe. Incubation of the gastric (HR) or renal cell carcinoma (RCC) cell lines, but not of other IL2R+ carcinoma cell lines or normal keratinocytes, in the presence of IL2 resulted in dose-dependent inhibition of tumor cell growth. Monoclonal antibodies (MAbs) specific for IL2R-beta chain completely reversed this growth inhibitory effect of IL2. The ligand, IL2, also down-regulated surface expression of its own receptor and of intercellular adhesion molecule-I (ICAM-I) or class I major histocompatibility complex (MHC) antigens on IL2R+ tumor cells. All carcinoma cells studied incubated in the presence of IL2 exhibited significantly increased sensitivity to growth-inhibitory effects of other cytokines such as interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha or transforming growth factor (TGF)-beta. IL2 inhibited growth of the HR cells by arresting a significant proportion of tumor cells in the G0/G1 phase of the cell cycle. Thus, IL2 can have direct effects on IL2R+ carcinoma cells, leading to changes in growth or to increases in sensitivity of tumor cells to cytostatic activities of other cytokines.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, PA 15213.
authors.forename: S
authors.initials: S
authors.lastname: Yasumura
authors.forename: W C
authors.initials: WC
authors.lastname: Lin
authors.forename: E
authors.initials: E
authors.lastname: Weidmann
authors.forename: P
authors.initials: P
authors.lastname: Hebda
authors.forename: T L
authors.initials: TL
authors.lastname: Whiteside
mesh_terms: D000951:Antigens, Neoplasm / Q000502:physiology; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D017403:In Situ Hybridization; D007376:Interleukin-2 / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000648:ultrastructure; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D012194:RNA-Directed DNA Polymerase