CONSTITUTIVE PRODUCTION OF IL-2 BY HUMAN CARCINOMA-CELLS, EXPRESSION OF IL-2 RECEPTOR, AND TUMOR-CELL GROWTH

Human carcinomas spontaneously express abundant IL-2R beta but little IL-2R alpha on the cell surface, contain mRNA for IL-2R beta- and IL-2 R alpha-chains, and may be inhibited in growth by exogenous IL-2. To s tudy the relationship between IL-2R expression and growth inhibition b y IL-2, carcinoma cells were transduced with IL-2R alpha and IL-2R gam ma cDNAs or IL-2R beta antisense cDNA. Transfectants with the IL-2R al pha gene expressed high levels of the alpha- and beta-receptor chains and showed increased binding of [I-125]IL-2. Exogenous IL-2 at the pic ometer concentrations inhibited their growth, and Abs to IL-2R alpha- or IL-2R beta-chains reversed the inhibition. After transduction of IL -2R beta antisense cDNA, gastric carcinoma (HR) cells no longer expres sed IL-2R beta-chain, and their proliferation was depressed in the abs ense of exogenous IL-2. Transduction of IL-2R gamma-chain cDNA into tu mor cells increased sensitivity to growth inhibition by exogenous IL-2 of a squamous cell carcinoma line, but not of HR or renal cell carcin oma lines. All of the parental and transduced tumor cell lines were fo und to constitutively express intracellular IL-2, detectable by immuno staining or flow cytometry of permeabilized cells. IL-2 was present on the surface of some tumor cells. Intracellular IL-2R beta and IL-2R g amma proteins were also detectable in tumor cells. Using reverse-trans cription PCR combined with Southern blots or in situ hybridization, mR NA for IL-2 was found to be present in parental and transduced tumor c ells. Expression on human carcinomas of IL-2R beta, inhibition of thei r growth by IL-2R beta antisense cDNA, and their ability to constituti vely produce IL-2 and its presence on the cell surface, all suggest th at endogenous IL-2 may play a role in tumor cell growth.