Interaction of tumor cells with vascular endothelia: role of platelet-activating factor.
We investigated whether tumor cell/endothelia interaction can be influenced by platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a lipid mediator that promotes adhesiveness and extravasation of leukocytes in the inflammatory reaction. We found that the PAF receptor antagonist WEB 2086 prevents adhesion of melanoma Hs294T and colon carcinoma LS180 lines to IL-1-stimulated endothelial cells. Moreover, PAF stimulated the adhesiveness of Hs294T and LS180 cells to VCAM-1 and E- selectin, respectively, in an artificial model consisting of recombinant adhesive proteins bound to protein A-coated substrata. Thus, tumoral and not endothelial cell surface seems to be involved in the PAF-mediated enhancement of tumor cell adhesiveness to IL-1-activated endothelia. This observation is supported by the finding that Hs294T and LS180 cells express high affinity and functionally active receptors for PAF. By using specific inhibitors, we found that PAF-induced enhancement of cell adhesiveness was mediated by G-protein activation and protein tyrosine phosphorylation. In addition, protein tyrosine phosphorylation was observed in Hs294T and LS180 cells stimulated by PAF. In conclusion, we demonstrated that PAF-mediated activation of tumor cells enhances their adhesiveness to IL-1-stimulated vascular endothelia.
Mannori
G
G
Department of Experimental Pathology and Oncology, University of Florence, Italy.
Barletta
E
E
Mugnai
G
G
Ruggieri
S
S
D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017931:DNA Primers; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D017931:DNA Primers; D019040:E-Selectin; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D019010:Vascular Cell Adhesion Molecule-1; C039351:platelet activating factor receptor