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.

Serum soluble interleukin-2 receptor level as a prognostic indicator in gastric cancer

“…Recently, it has been reported that various carcinoma cell lines express the a-and 5-chains of IL-2R (Yasumura et al, 1994). In our study, the serum levels of sIL-2R were elevated according to the extent of the gastric tumour, raising the possibility that sIL-2R was produced by the tumour cells.…”

Interleukin-2 expression in human carcinoma cell lines and its role in cell cycle progression

“…The IL-2R appears to be expressed not only on hematopoietic cells but also on a wide variety of non-hematopoietic cells, including normal and malignant cells of the epithelial origin (Saneto et al, 1986;Weidmann et al, 1992;Plaisance et al, 1992Plaisance et al, , 1993Artz et al, 1992;Alileche et al, 1993;Ciacci et al, 1993;Yasumura et al, 1994;Lin et al, 1995;McMillan et al, 1995). Functions of the IL-2R chains in nonhematopoietic cells are not fully understood.…”

“…Functions of the IL-2R chains in nonhematopoietic cells are not fully understood. Binding of exogenous recombinant IL-2 to the IL-2R complex on these cells has been variously reported to enhance, decrease or not a ect cell proliferation (Saneto et al, 1986;Weidmann et al, 1992;Yasumura et al, 1994;McMillan et al, 1995). In addition, exogenous IL-2 was shown to induce changes in expression of surface markers (ICAM-1, HLA class I, HLA-DR and CD44) known to be associated with tumor progression Plaisance et al, 1993).…”

“…We have reported previously that human carcinomas spontaneously express abundant IL-2Rb, IL-2Rg and very little IL-2Ra on the cell surface, contain mRNA for these receptor chains, and are inhibited in growth by high molar concentrations of exogenously-delivered IL-2 in vitro and in vivo, in a xenograft model of tumor growth in nude mice (Rabinowich et al, 1992;Weidmann et al, 1992;Yasumura et al, 1994;Lin et al, 1995). Others have reported expression of IL-2Ra-and b-chains on a variety of normal and malignant cells, including human embryonic ®broblasts , melanoma cells (Rimoldi et al, 1993), pituitary cells (Artz et al, 1992), or intestinal epithelial cells (Ciacci et al, 1993).…”

Tyrosine-kinase expression profiles in human gastric cancer cell lines and their modulations with retinoic acids

“…The cells were then washed with serum-free medium and maintained in serum-free culture medium with the presence or absence of RA for 36 -48 h. The final concentration of RA used in the medium was 10 À6 -10 À8 M and the concentration of DMSO in control groups was 0.1%. The growth response of RA-treated cells was measured by an MTT assay (Yasumura et al, 1994).…”