Plaisance S, Rubinstein E, Alileche A, Han D S, Sahraoui Y, Mingari M C, Bellomo R, Rimoldi D, Colombo M P, Jasmin C
Unité INSERM 268, Hôpital Paul Brousse, Villejuif, France.
Int J Cancer. 1993 Aug 19;55(1):164-70. doi: 10.1002/ijc.2910550129.
Flow cytometric analysis reveals that 5 human melanoma cell lines (M14, IGR3, ME1477, JUSO, GLL19) express both alpha and beta chain of the interleukin 2 receptor (IL-2R alpha and IL-2R beta). These chains are able to specifically bind IL-2 and to form high-affinity heterodimers (IL-2R alpha beta). Analysis of poly A+ RNAs by Northern blot reveals the presence of typical transcripts for both the IL-2R alpha gene (3.6 kb) and the IL-2R beta gene (4 kb). Reverse transcription/polymerase chain reaction analysis allowed transcripts for the IL2R gamma (p64) gene to be detected in 3 of these melanoma cell lines (M14, IGR3, ME 1477). Incubation with human recombinant IL-2 modifies in IL-2R alpha+beta+gamma+ (M14) the expression of several surface molecules: down-regulation of ICAM-1, HLA class I and HLA-DR and up-regulation of CD44. IL-2 is also active on IL-2 alpha+beta+gamma- cell lines since it decreases ICAM-1 and HLA class-II expression at the surface of JUSO cells. Down-regulation of ICAM-1, whose expression in melanoma cells is a marker of tumor progression, is detectable within 3 hr in M14 cells and is maximal after 48 hr incubation, at IL-2 concentrations corresponding to the high-affinity heterodimers. This feature is specific since it is partially inhibited by MAbs directed against the IL-2 binding site of the IL-2R alpha (MAR93, 10T14) and IL-2R beta (MiK beta 1, TU27) chains. Our data support the notion of a direct effect of IL-2 on human melanoma cells. Modulation of the expression of surface molecules which is important for the interaction with immunocompetent cells or for tumor progression, could have a role to play during in vivo IL-2 treatment of human melanomas.
流式细胞术分析显示，5种人黑色素瘤细胞系（M14、IGR3、ME1477、JUSO、GLL19）表达白细胞介素2受体的α链和β链（IL-2Rα和IL-2Rβ）。这些链能够特异性结合IL-2并形成高亲和力异二聚体（IL-2Rαβ）。通过Northern印迹分析多聚A+RNA，发现IL-2Rα基因（3.6 kb）和IL-2Rβ基因（4 kb）均存在典型转录本。逆转录/聚合酶链反应分析在其中3种黑色素瘤细胞系（M14、IGR3、ME 1477）中检测到了IL2Rγ（p64）基因的转录本。用人重组IL-2孵育可改变IL-2Rα+β+γ+（M14）中几种表面分子的表达：细胞间黏附分子-1（ICAM-1）、I类人白细胞抗原（HLA class I）和HLA-DR下调，而CD44上调。IL-2对IL-2α+β+γ-细胞系也有活性，因为它可降低JUSO细胞表面ICAM-1和II类HLA的表达。ICAM-1在黑色素瘤细胞中的表达是肿瘤进展的标志物，其下调在M14细胞中3小时内即可检测到，在48小时孵育后达到最大程度，此时IL-2浓度对应高亲和力异二聚体。这一特性具有特异性，因为它部分受到针对IL-2Rα（MAR93、10T14）和IL-2Rβ（MiKβ1-TU27）链的IL-2结合位点的单克隆抗体的抑制。我们的数据支持IL-直接作用于人类黑色素瘤细胞的观点。表面分子表达的调节对于与免疫活性细胞的相互作用或肿瘤进展很重要，可能在体内用IL-2治疗人类黑色素瘤过程中发挥作用。
