EXPRESSION OF INTERLEUKIN-2 RECEPTORS ON HUMAN CARCINOMA CELL-LINES AND TUMOR-GROWTH INHIBITION BY INTERLEUKIN-2

We have previously shown that human squamous cell carcinomas (SCC) exp ressed the interleukin 2 receptor (IL2R)-alpha and -beta chains, and t hat the ligand, IL2, directly inhibits growth of the tumor in vitro an d 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 car cinoma cell lines and on normal human keratinocytes in early-stage cul tures. While all carcinoma cells in a population expressed IL2R-alpha and -beta proteins, in keratinocytes obtained from different normal do nors, variable proportions of cells were positive, as measured by flow cytometry. The carcinoma lines and 2/5 keratinocyte lines studied wer e also found to contain transcripts for the IL2R-gamma chain detectabl e by combined reverse transcription-PCR (RT-PCR) and hybridization wit h the specific cDNA probe. Incubation of the gastric (HR) or renal cel l carcinoma (RCC) cell lines, but not of other IL2R(+) carcinoma cell lines or normal keratino-cytes, in the presence of IL2 resulted in dos e-dependent inhibition of tumor cell growth. Monoclonal antibodies (MA bs) specific for IL2R-beta chain completely reversed this growth inhib itory effect of IL2. The ligand, IL2, also down-regulated surface expr ession of its own receptor and of intercellular adhesion molecule-1 (I CAM-1) or class 1 major histocompatibility complex (MHC) antigens on I L2R(+) tumor cells. All carcinoma cells studied incubated in the prese nce of IL2 exhibited significantly increased sensitivity to growth-inh ibitory effects of other cytokines such as interferon (IFN)-gamma, tum or necrosis factor (TNF)-alpha or transforming growth factor (TGF)-bet a. IL2 inhibited growth of the HR cells by arresting a significant pro portion of tumor cells in the G(0)/G(1) phase of the cell cycle. Thus, IL2 can have direct effects on IL2R(+) carcinoma cells, leading to ch anges in growth or to increases in sensitivity of tumor cells to cytos tatic activities of other cytokines. (C) Wiley-Liss, Inc.