Tumour-derived interleukin 1alpha (IL-1alpha) up-regulates the release of soluble intercellular adhesion molecule-1 (sICAM-1) by endothelial cells

Br J Cancer. 1997;76(10):1255-61. doi: 10.1038/bjc.1997.545.


Levels of circulating soluble intercellular adhesion molecule-1 (sICAM-1) are elevated in patients affected by solid malignancies; however, the cellular sources generating high levels of sICAM-1 remain to be characterized. Using conditioned media (CM) from seven ICAM-1-positive or -negative neoplastic cells, we demonstrate that tumour-derived interleukin 1alpha (IL-1alpha) significantly (P < 0.05) up-regulates the release of sICAM-1 by human umbilical vein endothelial cells. The intensity of the effect correlated with the amounts of IL-1alpha detectable in CM. Levels of ICAM-1 mRNA were also up-regulated by tumour-secreted IL-1alpha. The up-regulation of the shedding of sICAM-1 and of its expression at protein and mRNA level were completely reversed by the addition of anti-IL-1alpha neutralizing antibodies. Consistent with the in vitro data, tumour endothelia were strongly stained for ICAM-1 compared with autologous normal tissue endothelia. Taken altogether, our observations reveal an IL-1alpha-mediated tumour-endothelium relationship sustaining the shedding of sICAM-1 by endothelial cells. This is a general phenomenon in solid malignancies that correlates with the ability of neoplastic cells to secrete IL-1alpha rather than with their expression of ICAM-1 and/or histological origin. sICAM-1 has been previously shown to inhibit LFA-1/ICAM-1-mediated cell-cell interactions; therefore, the ability of neoplastic cells to secrete IL-1alpha is likely to represent a mechanism for their escape from immune interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Culture Media, Conditioned
  • Endothelium, Vascular / metabolism*
  • Humans
  • Intercellular Adhesion Molecule-1 / analysis
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Interleukin-1 / physiology*
  • Neoplasms / immunology*
  • Up-Regulation
  • Urinary Bladder Neoplasms / chemistry


  • Culture Media, Conditioned
  • Interleukin-1
  • Intercellular Adhesion Molecule-1