Expression of interleukin 2 receptors on human carcinoma cell lines and tumor growth inhibition by interleukin 2

Publisher Website
Google Scholar
Abstract
We have previously shown that human squamous cell carcinomas (SCC) express the interleukin 2 receptor (IL2R)‐α and ‐β 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 α and β 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‐α and ‐β 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‐γ 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‐β 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)‐γ, tumor necrosis factor (TNF)‐α or transforming growth factor (TGF)‐β. IL2 inhibited growth of the HR cells by arresting a significant proportion of tumor cells in the Go/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.