Interleukin-2 enhances the growth of human melanoma cells derived form primary but not from metastatic tumours.
Previously, we demonstrated that in vitro treatment of B16F10 murine melanoma cells with interleukin-2 (IL-2) enhances proliferation and metastasis. To further investigate the role played by IL-2 in human melanomas, we studied the expression of IL-2/IL-2 receptor and the effect of IL-2 on the proliferation of melanoma cell lines derived from primary (A375 and RMS cell lines) and metastatic (Hs294T cell line) tumours. We found a constitutive expression of cytoplasmic IL-2 and alpha, beta and gamma-subunits of the IL-2R on the surface of the three melanoma cell lines. The presence of IL-2 in the culture increased the proliferation rate in A375 and RMS cell lines, but no effect was observed in Hs294T metastatic cells. Biologically active IL-2 could be found in the supernatant of the three melanoma cell lines, particularly in A375 and RMS cells, in which an inhibition of the proliferation rate was observed when IL-2 was blocked. Moreover, the combination of anti-IL-2R beta and anti-IL-2R gamma blocking antibodies induced a significant down-regulation of cell proliferation in the three melanoma cell lines, and the combination of anti-IL-2R alpha, anti-IL-2R beta and anti-IL-2R gamma blocking antibodies inhibited IL-2-mediated growth stimulation in A375 and Hs294T cell lines. In RMS cells, a more significant effect was observed when only IL-2R gamma was blocked. Finally, exogenous IL-2 modulated the IL-2 endogenously produced by melanoma cells. These data show that IL-2 may modulate the growth of melanoma cells through autocrine or/and paracrine mechanisms.
García-Vázquez
M D
MD
Department of Cell Biology and Morphological Sciences, School of Medicine and Dentistry, University of the Basque Country, Leioa 48940, Bizkaia, Spain.
Boyano
M D
MD
Cañavate
M L
ML
Gardeazabal
J
J
de Galdeano
A G
AG
López-Michelena
T
T
Ratón
J A
JA
Izu
R
R
Díaz-Ramón
J L
JL
Díaz-Pérez
J L
JL
D000911:Antibodies, Monoclonal / Q000276:immunology; D019898:Autocrine Communication; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D009362:Neoplasm Metastasis; D015375:Receptors, Interleukin-2 / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins