E-SELECTIN EXPRESSION INDUCED BY PANCREAS-CARCINOMA-DERIVED INTERLEUKIN-1-ALPHA RESULTS IN ENHANCED ADHESION OF PANCREAS-CARCINOMA CELLS TOENDOTHELIAL-CELLS

Cellular adhesion of sialyl-Lewis-a(SLe(a))-positive pancreas carcinom a to endothelial cells (EC) is augmented by activation of EC via up-re gulated E-selectin expression on EC. Cocultivation of pancreas-carcino ma 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 expressi on on the endothelial-cell surface, augmenting SLe(a)-positive pancrea s-carcinoma cell attachment with HUVEC. Culture supernatants of 6 test ed pancreas-carcinoma cell lines contained soluble, E-selectin-inducin g factor(s). The E-selectin-inducing effect by the supernatants was bl ocked by the protein-kinase-C inhibitor, H7. Antibodies against SLe(a) and E-selectin but not SLe(x) or ICAM-1 blocked the increased pancrea s-carcinoma-to-endothelial attachment. Paraformaldehyde(PFA)-fixed PCI -24 cells also induced E-selectin on vascular endothelial cells upon d irect contact with endothelial cells, indicating the presence of a mem brane-bound form. The 6 pancreas-carcinoma lines all produced IL-1 alp ha mRNA and protein but not IL-1 beta or TNF-alpha protein and/or mRNA . Absorption of IL-1 alpha from the supernatants by IL-1 alpha-specifi c antibody almost completely abolished E-selectin-inducing activity. A nti-IL-1 alpha antibody also abolished the E-selectin-inducing activit y of PFA-fixed PCI. IL-1 alpha production by PCI cells was up-regulate d by TNF-alpha. These observations suggest that substance(s) produced by pancreas-carcinoma cells, in this case, IL-1 alpha may contribute t o pancreas-carcinoma-cell colonization in non-inflamed, distant locati ons in vivo, by activating vascular endothelial cells. (C) 1995 Wiley- Liss. Inc.