E‐selectin expression induced by pancreas‐carcinoma‐derived interleukin‐1α results in enhanced adhesion of pancreas‐carcinoma cells to endothelial cells

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Abstract
Cellular adhesion of sialyl‐Lewis‐a(SLea)‐positive pancreas carcinoma to endothelial cells (EC) is augmented by activation of EC via up‐regulated E‐selectin expression on EC. Co‐cultivation of pancreas‐carcinoma cells, PCI‐24, with human umbilical‐vein endothelial cells (HUVEC) for 5 hr at the PCI‐to‐HUVEC ratio of 1:10 induced E‐selectin expression on the endothelial‐cell surface, augmenting SLea‐positive pancreas‐carcinoma cell attachment with HUVEC. Culture supernatants of 6 tested pancreas‐carcinoma cell lines contained soluble, E‐selectin‐inducing factor(s). The E‐selectin‐inducing effect by the supernatants was blocked by the protein‐kinase‐C inhibitor, H7. Antibodies against SLea and E‐selectin but not SLex or ICAM‐I blocked the increased pancreas‐carcinoma‐to‐endothelial attachment. Paraformaldehyde(PFA)‐fixed PCI‐24 cells also induced E‐selectin on vascular endothelial cells upon direct contact with endothelial cells, indicating the presence of a membrane‐bound form. The 6 pancreas‐carcinoma lines all produced IL‐1α mRNA and protein but not IL‐1β or TNF‐α protein and/or mRNA Absorption of IL‐lα from the supernatants by IL‐lα‐specific antibody almost completely abolished E‐selectin‐inducing activity. Anti‐IL‐lα antibody also abolished the E‐selectin‐inducing activity of PFA‐fixed PCI. IL‐1α production by PCI cells was up‐regulated by TNF‐α. These observations suggest that substance(s) produced by pancreas‐carcinoma cells, in this case, IL‐1α, may contribute to pancreas‐carcinoma‐cell colonization in non‐inflamed, distant locations in vivo, by activating vascular endothelial cells.