Retroviral transduction of intercellular adhesion molecule-1 enhances endothelial attachment of bladder cancer.
An intercellular adhesion molecule-1 (ICAM-1)-negative RT4 transitional cell carcinoma (TCC) cell line was transduced with full-length ICAM-1 cDNA via a retroviral vector. Flow cytometry showed that a sense-oriented clone (S20) highly expressed ICAM-1 while an anti-sense clone (AS6) did not. Both S20 and AS6 bound with equal frequency (30 +/- 8.7% vs 30 +/- 9.4%) to unstimulated human umbilical vein endothelial cells (HUVECs) in cell attachment assays. However, when phorbol myristate acetate (PMA)-activated T lymphocytes, which express lymphocyte function-associated antigen-1 (LFA-1), were cocultured with tumor cells, attachment of S20 increased twofold (60 +/- 11.9%) but AS6 showed no change (32 +/- 11%). Blocking studies with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies caused an inhibition of the attachment to baseline levels, demonstrating that the enhancement of S20 attachment was dependent upon the LFA-1/ICAM-1 interaction. Enhanced attachment of S20 was not inhibited by the addition of isotypic immunoglobulin G. These results suggest that LFA-1-expressing leukocytes may act as a bridge between the endothelium and tumor cells which express ICAM-1 and, thereby, enhance the potential for hematogenous metastasis.
Tanabe
K
K
The Cleveland Clinic Foundation, Department of Urology, OH 44195, USA.
Alexander
J P
JP
Steinbach
F
F
Campbell
S
S
Novick
A C
AC
Klein
E A
EA
D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D009362:Neoplasm Metastasis; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*
D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1