Human melanoma cells express a functional interleukin-2 receptor.
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.
Plaisance
S
S
Unité INSERM 268, Hôpital Paul Brousse, Villejuif, France.
Rubinstein
E
E
Alileche
A
A
Han
D S
DS
Sahraoui
Y
Y
Mingari
M C
MC
Bellomo
R
R
Rimoldi
D
D
Colombo
M P
MP
Jasmin
C
C
D000951:Antigens, Neoplasm / Q000096:biosynthesis; D000954:Antigens, Surface / Q000096:biosynthesis; D001483:Base Sequence; D015152:Blotting, Northern; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta