RETROVIRAL TRANSDUCTION OF INTERCELLULAR-ADHESION MOLECULE-1 ENHANCESENDOTHELIAL ATTACHMENT OF BLADDER-CANCER

An intercellular adhesion molecule-1 (ICAM-1)negative RT4 transitional cell carcinoma (TCC) cell line was transducted with full-length ICAM- 1 cDNA via a retroviral vector. Flow cytometry showed that a sense-ori ented clone (S20) highly expressed ICAM-1 while an anti-sense clone (A S6) 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 a cetate (PMA)-activated T lymphocytes, which express lymphocyte functio n-associated antigen-1 (LFA-1), were cocultured with tumor cells, atta chment of S20 increased twofold (60 +/- 11.9%) but AS6 showed no chang e (32 +/- 11%). Blocking studies with anti-LFA-l and anti-ICAM-1 monoc lonal antibodies caused an inhibition of the attachment to baseline le vels, demonstrating that the enhancement of S20 attachment was depende nt upon the LFA-1/ICAM-1 interaction. Enhanced attachment of S20 was n ot inhibited by the addition of isotypic immunoglobulin G. These resul ts suggest that LFA-l-expressing leukocytes may act as a bridge betwee n the endothelium and tumor cells which express ICAM-1 and, thereby, e nhance the potential for hematogenous metastasis.