Influence of tumor-derived interleukin 1 on melanoma-endothelial cell interactions in vitro.
Human melanoma cell lines that express high constitutive levels of the metastasis-associated marker intercellular adhesion molecule 1 (ICAM-1) were found to secrete interleukin 1 (IL-1) in vitro. Experiments with neutralizing antibodies showed that this cytokine was responsible for their expression of ICAM-1 but not that of two other progression/metastasis markers, Muc-18 and Gp IIb/IIIa. The IL-1 present in melanoma-conditioned medium induced the expression of vascular cell adhesion molecule 1, endothelial-leukocyte adhesion molecule 1, and ICAM-1 on human umbilical vein endothelial cells (ECs) in culture and increased the rate at which melanoma cells and ECs adhered to each other. IL-1-producing melanoma lines adhered significantly more rapidly to ECs than did non-IL-1-producing lines, and this enhancement was reduced by prior incubation of the melanoma cells with neutralizing anti-IL-1 antibodies. Similarly, endothelial cells treated with conditioned medium from IL-1-producing melanoma lines adhered significantly more rapidly to melanoma cells than did ECs treated with medium from non-IL-1-producing melanoma lines, and this enhancement was abolished by addition of anti-IL-1 antibodies to EC cultures in conditioned medium. Blocking antibodies to endothelial vascular cell adhesion molecule 1, endothelial-leukocyte adhesion molecule 1, and ICAM-1 failed to inhibit melanoma-EC adhesion, but an antibody to tumor cell GpIIb/IIIa did block adhesion by up to 44%. The ability to secrete IL-1 could increase the metastatic potential of melanoma cells by stimulating tumor cell-EC adhesion.
Drug Targeting, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, England.
F J
FJ
Burrows
D O
DO
Haskard
I R
IR
Hart
J F
JF
Marshall
S
S
Selkirk
S
S
Poole
P E
PE
Thorpe
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051929:CD146 Antigen; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects*; D004727:Endothelium / Q000166:cytology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D008562:Membrane Glycoproteins / Q000502:physiology; D019006:Neural Cell Adhesion Molecules; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051929:CD146 Antigen; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D010980:Platelet Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1