title: E-selectin expression induced by pancreas-carcinoma-derived interleukin-1 alpha results in enhanced adhesion of pancreas-carcinoma cells to endothelial cells.
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-1 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-1 alpha 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-specific antibody almost completely abolished E-selectin-inducing activity. Anti-IL-1 alpha antibody also abolished the E-selectin-inducing activity of PFA-fixed PCI. IL-1 alpha production by PCI cells was up-regulated by TNF-alpha. These observations suggest that substance(s) produced by pancreas-carcinoma cells, in this case, IL-1 alpha, may contribute to pancreas-carcinoma-cell colonization in non-inflamed, distant locations in vivo, by activating vascular endothelial cells.
authors.affiliation: Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kaji
authors.forename: H
authors.initials: H
authors.lastname: Ishikura
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
authors.forename: M
authors.initials: M
authors.lastname: Omi
authors.forename: A
authors.initials: A
authors.lastname: Ishizu
authors.forename: C
authors.initials: C
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Yoshiki
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D018395:CA-19-9 Antigen; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002450:Cell Communication; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000302:isolation & purification / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000473:pathology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
chemical_list: D018395:CA-19-9 Antigen; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D019040:E-Selectin; D005732:Gangliosides; D007375:Interleukin-1; D007546:Isoquinolines; D009363:Neoplasm Proteins; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C064564:sialyl Le(a) ganglioside; D011493:Protein Kinase C