Yasumura S, Lin W C, Weidmann E, Hebda P, Whiteside T L
Department of Pathology, University of Pittsburgh School of Medicine, PA 15213.
Int J Cancer. 1994 Oct 15;59(2):225-34. doi: 10.1002/ijc.2910590215.
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.
我们之前已经表明，人类鳞状细胞癌（SCC）表达白细胞介素2受体（IL2R）的α链和β链，并且配体IL2在体外和体内的肿瘤异种移植裸鼠模型中可直接抑制肿瘤生长。我们现在表明，IL2R的α链和β链在多种人类癌细胞系以及早期培养的正常人类角质形成细胞上表达。虽然群体中的所有癌细胞都表达IL2R-α和-β蛋白，但通过流式细胞术检测发现，从不同正常供体获得的角质形成细胞中，阳性细胞的比例各不相同。通过逆转录聚合酶链反应（RT-PCR）结合与特异性cDNA探针杂交，还发现所研究的癌细胞系和2/5角质形成细胞系含有IL2R-γ链的转录本。在IL2存在的情况下，胃（HR）或肾细胞癌（RCC）细胞系（而非其他IL2R +癌细胞系或正常角质形成细胞）的孵育导致肿瘤细胞生长受到剂量依赖性抑制。针对IL2R-β链的单克隆抗体（MAb）完全逆转了IL2的这种生长抑制作用。配体IL2还下调了其自身受体以及IL2R +肿瘤细胞上细胞间黏附分子-I（ICAM-I）或I类主要组织相容性复合体（MHC）抗原的表面表达。在IL2存在下孵育的所有研究癌细胞对其他细胞因子如干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α或转化生长因子（TGF）-β的生长抑制作用表现出显著增强的敏感性。IL2通过使相当比例的肿瘤细胞停滞在细胞周期的G0/G1期来抑制HR细胞的生长。因此，IL2可对IL2R +癌细胞产生直接影响，导致生长变化或肿瘤细胞对其他细胞因子细胞抑制活性的敏感性增加。
