Fibrinogen mediates bladder cancer cell migration in an ICAM-1-dependent pathway.
Fibrinogen (fg), present in tumor matrices, has been demonstrated to be determinant in metastatic potential. We have recently shown that fg/ICAM-1 interactions are involved in leukocyte migration across endothelial cell monolayers. Using bladder transitional cell carcinoma as a model, we will show in this study that bladder high grade tumor cell lines express ICAM-1, and that this expression induces an fg-mediated migration. This phenomenon was dependent on ICAM-1/fg interaction as well as RhoA activity. ICAM-1 was concentrated in focal adhesion plaques when tumor cells were allowed to adhere on immobilized fg, suggesting a role in cell migration. The addition of fg induced a 3- to 6-fold enhancement of bladder tumor cell migration through HUVEC monolayers. This process was inhibited by an anti-ICAM-1 antibody blocking fg binding, demonstrating that ICAM-1/fg interaction was involved in the extravasation process. Finally, immunohistological studies revealed that the expression of ICAM-1 was closely associated with an infiltrative histological phenotype.
Roche
Yann
Y
Unité INSERM 578, Institut Albert Bonniot, Grenoble, France.
Pasquier
Dominique
D
Rambeaud
Jean-Jacques
JJ
Seigneurin
Daniel
D
Duperray
Alain
A
D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology; D005340:Fibrinogen / Q000378:metabolism / Q000502:physiology*; D022001:Focal Adhesions; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D011485:Protein Binding; D014471:Umbilical Veins / Q000166:cytology; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen; D020742:rhoA GTP-Binding Protein