The role of human melanoma cell ICAM-1 expression on lymphokine activated killer cell-mediated lysis, and the effect of retinoic acid

Intercellular adhesion molecule (ICAM-1) exists as a membrane-associated fo rm (mICAM-1) on the surface of tumour cells as well as a soluble form (sICA M-1). This study analyses the ability of all-trans retinoic acid (RA) to al ter both sICAM and mlCAM-1 expression in C8161 and Hs294T human melanoma ce ll lines and investigates the involvement of ICAM-1 in the interaction betw een tumour and lymphokine-activated killer (LAK) cells using the Cr-51 rele ase assay. Our data showed that 4-day pretreatment of the tumour cells with 10(-7) M RA and 10(-6) M RA induced an increase in lysis of both cell line s and also increased mICAM-1 expression without having any effect on sICAM- 1 levels. Addition of blocking ICAM-1 antibody (10 mu g ml(-1)) to-the C816 1 cells at an effector:tumour cell ratio of 40:1 caused a 2.3-fold reductio n in lysis of tumour cells and a 3-fold reduction in lysis of RA-treated ce lls. Blocking ICAM-1 antibody at optimum concentrations of 5 mu g ml(-1) re duced lysis 1.8-fold in control Hs294T cells and 1.3-fold in RA-treated cel ls. Blocking the HLA-ABC complex had no effect on lysis. The more highly me tastatic C8161 cells were found to secrete 4-fold greater levels of sICAM-1 than the poorly metastatic Hs294T cells and addition of sICAM-1 to the ass ay failed to affect lysis of either cell line but did induce a 2-fold decre ase in lysis of RA-treated C8161 cells. Collectively, these data provide fu rther evidence for ICAM-1 involvement in the tumour/LAK cell response and i ndicates that the RA-induced increase in mICAM-1 levels are partly responsi ble for the increase in susceptibility of the tumour cells, sICAM-1 appears to be unimportant in evasion of the tumour cells from LAK cell lysis, but may play a role in evasion of RA-treated C8161 cells.