The association of sialyl Lewis(a) antigen with the metastatic potential of human colon cancer cells

Anticancer Res. Sep-Oct 1997;17(5A):3505-11.

Abstract

Background: The vascular endothelium plays a critical role in cancer metastasis by directing circulating cancer cells into extravascular tissues and by expressing cell adhesion molecules. The authors investigated the interaction between a cell line derived from human colon cancer and cultured murine endothelial cells, in vitro, and in vivo.

Materials and methods: Variant cell lines with high (WiDr-HA) or low (WiDr-LA) levels of cell surface sialyl Lewis(a) antigen (s-Le(a)) were isolated from the heterogeneous WiDr cells (WiDr-P) in order to characterize the biological behavior of colon cancer cells having elevated cell surface contents of s-Le(a).

Results: A correlation was found to exist between the degree of s-Le(a) expression, and the attachment of cancer cells to activated human umbilical vein endothelial cells, or to F-2 cells isolated from murine vascular endothelial cells. The adhesion of WiDr-P and WiDr-HA to F-2 cells was inhibited by the addition of anti-s-Le(a) antibody (Ab). WiDr-P and WiDr-HA both demonstrated the capacity to metastasize to the liver, by the inoculation of cancer cells to the spleen, while WiDr-LA did not do so. The number of metastatic nodules of WiDr-HA was significantly higher than that of WiDr-P. Treatment with anti-s-Le(a) Ab inhibited the metastasis of WiDr-P and WiDr-HA to the liver, but not with anti-s-Le(x) Ab.

Conclusions: These findings suggest that s-Le(a) plays an important role in cell adhesion molecules, in the metastasis of colon cancer.

MeSH terms

  • Animals
  • CA-19-9 Antigen
  • Cell Adhesion / drug effects
  • Colonic Neoplasms / pathology*
  • E-Selectin / metabolism
  • Endothelium, Vascular / metabolism
  • Gangliosides / metabolism*
  • Humans
  • Interleukin-1 / pharmacology
  • Liver Neoplasms / secondary
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis*
  • Spleen / pathology

Substances

  • CA-19-9 Antigen
  • E-Selectin
  • Gangliosides
  • Interleukin-1
  • sialyl Le(a) ganglioside