Cytomegalovirus-infected neuroblastoma cells exhibit augmented invasiveness mediated by beta1alpha5 integrin (VLA-5)

Tissue Antigens. 2000 May;55(5):412-21. doi: 10.1034/j.1399-0039.2000.550503.x.

Abstract

Previously, experimental in vivo results showed that the productively and persistently human cytomegalovirus (HCMV)-infected neuroblastoma cell line UKF-NB-4AD169 exhibits a more malignant phenotype than the non-infected variant UKF-NB-4. To prove the assumption that enhanced malignancy may be due to enhanced invasive potential of the infected cells we studied interactions of both lines with monolayers of cultured endothelial cells. UKF-NB-4AD169 cells adhered to and transmigrated through endothelial monolayer to a significantly higher extent compared with UKF-NB4. Furthermore, the adhesion of UKF-NB-4AD169 but not of UKF-NB4 resulted in focal disruption of the monolayer integrity which facilitates tumor cell transmigration. Blocking antibodies directed against the beta1 integrin chain as well as beta1alpha5 on the tumor cells specifically inhibited adhesion in a concentration-dependent manner. When UKF-NB-4 were pretreated with a beta1 integrin activating antibody, focal disruption of the endothelial integrity also occurred. These findings lead us to suggest that HCMV infection activates beta1alpha5 in the host neuroblastoma cell which in turn enables these cells to tightly adhere to endothelial cells. In the presence of the protease inhibitor phenantroline, beta1alpha5-mediated adhesion was not impaired whereas UKF-NB4AD169-mediated endothelial monolayer permeabilization was dose dependently inhibited. We conclude that human cytomegalovirus infection contributes to augmented neuroblastoma invasiveness via adhesion of activated beta1alpha5 and subsequent matrix digestion by proteases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Cell Adhesion / physiology
  • Cell Communication / physiology
  • Cell Movement / physiology
  • Cytomegalovirus Infections / pathology*
  • Cytomegalovirus*
  • E-Selectin / analysis
  • Epithelial Cells / chemistry
  • Epithelial Cells / cytology
  • Epithelial Cells / virology
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Intercellular Adhesion Molecule-1 / analysis
  • Membrane Glycoproteins / analysis
  • Neoplasm Invasiveness
  • Neuroblastoma / pathology*
  • Neuroblastoma / virology
  • Receptors, Fibronectin / analysis
  • Receptors, Fibronectin / immunology
  • Receptors, Fibronectin / metabolism*
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / virology
  • Umbilical Cord / cytology
  • Vascular Cell Adhesion Molecule-1 / analysis

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • E-Selectin
  • Membrane Glycoproteins
  • P-selectin ligand protein
  • Receptors, Fibronectin
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1