Tumor cell-endothelial interactions. Increased adhesion of human melanoma cells to activated vascular endothelium.
The authors examined the adhesion of seven human melanoma cell lines to cultured human umbilical vein endothelial cells (HEC) that were activated by cytokines or bacterial endotoxin. The adhesion of Hs 294T and MEL-24 cells was markedly increased (approximately 2 to 12-fold) after pretreatment of HEC monolayers for 6 hours with tumor necrosis factor, interleukin-1, or endotoxin. Smaller increases were noted with the cell lines RPMI 7951, HT 144, Malme-3M, MEL-2, and no significant increase was observed with MEL-5. Cytokine and endotoxin effects on melanoma-HEC adhesion were concentration- and time-dependent, with onset by 2 hours, peak at 6-8 hours and maintenance through 48 hours. Cytokine induction of increased HEC adhesiveness for melanoma cells was blocked by actinomycin-D or cycloheximide, suggesting the requirement for RNA and protein synthesis. Interaction of melanoma cells with subendothelial matrix did not appear to play a primary role because: 1) phase contrast and electron microscopy revealed direct contact between tumor cells and endothelial cells in standardized monolayer adhesion assays; 2) increased adhesion (rosette formation) of tumor cells to activated HEC was also observed after nonenzymatic resuspension of HEC, and 3) the matrix peptide GRGDSP partially blocked (approximately 45%) Hs 294T cell adhesion to subendothelial matrix, but had little or no effect on adhesion to activated HEC monolayers. Taken together, these data suggest that inducible HEC surface changes may mediate the adhesion of certain melanoma cells, thereby exerting an active influence over the metastatic process.
Rice
G E
GE
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Gimbrone
M A
MA
Bevilacqua
M P
MP
D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008545:Melanoma / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004731:Endotoxins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha