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

Int J Cancer. 1995 Mar 3;60(5):712-7. doi: 10.1002/ijc.2910600524.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • CA-19-9 Antigen
  • Carcinoma / chemistry
  • Carcinoma / pathology*
  • Cell Adhesion
  • Cell Adhesion Molecules / biosynthesis*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology
  • Cell Communication
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • E-Selectin
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Gangliosides / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interleukin-1 / isolation & purification
  • Interleukin-1 / pharmacology*
  • Isoquinolines / pharmacology
  • Neoplasm Proteins / isolation & purification
  • Neoplasm Proteins / pharmacology*
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / pathology*
  • Piperazines / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Stimulation, Chemical
  • Tumor Cells, Cultured
  • Umbilical Veins


  • CA-19-9 Antigen
  • Cell Adhesion Molecules
  • Culture Media, Conditioned
  • E-Selectin
  • Gangliosides
  • Interleukin-1
  • Isoquinolines
  • Neoplasm Proteins
  • Piperazines
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • sialyl Le(a) ganglioside
  • Protein Kinase C