Effects of endothelial cell treatment on 13-HODE and prostacyclin synthesis and its correlation with tumor cell-vascular endothelial cell adhesion.
Adhesion of tumor cells to vascular endothelial surfaces is one of the key steps in metastatic dissemination. Several factors are believed to be implicated in the regulation of the adhesive properties of tumor cells. We show that the adhesion of five different tumor cell lines, all of them of human origin, to human umbilical vascular endothelial cells (ECs) significantly increases following pretreatment of ECs with the cytokines interleukin-1 and tumor necrosis factor, whereas tumor cell/EC interactions remained unchanged after incubation with interferon-gamma. Significant augmentation in tumor cell adhesion was also observed when ECs were treated with the lipoxygenase inhibitors salicylate and the compound BW755C. In all cases, increased tumor cell adhesion was concomitant with significant decreases in the EC levels of linoleic acid, lipoxygenase-derived metabolite 13-hydroxy-octadecadienoic acid (13-HODE). On the contrary, pretreatment of the EC monolayers with aspirin did not result in any changes towards tumor cell adhesion. These results suggest that tumor cell/EC interaction is modulated, at least in part, by intracellular levels of 13-HODE and is independent of prostacyclin (PGI2) production by the ECs.
Bastida
E
E
Servicio de Hemoterapia y Hemostasia, Hospital Clinic, Universidad de Barcelona, España.
Almirall
L
L
Ordinas
A
A
Buchanan
M R
MR
Orr
F W
FW
Bertomeu
M C
MC
Haas
T A
TA
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008041:Linoleic Acids / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D008041:Linoleic Acids; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C024348:13-hydroxy-9,11-octadecadienoic acid; D015121:6-Ketoprostaglandin F1 alpha; D007371:Interferon-gamma; D011464:Epoprostenol