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 form (mICAM-1) on the surface of tumour cells as well as a soluble form (sICAM-1). This study analyses the ability of all-trans retinoic acid (RA) to alter both sICAM and mICAM-1 expression in C8161 and Hs294T human melanoma cell lines and investigates the involvement of ICAM-1 in the interaction between tumour and lymphokine-activated killer (LAK) cells using the Cr-51 release 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 lines and also increased mICAM-1 expression without having any effect on sICAM-1 levels. Addition of blocking ICAM-1 antibody (10 microg ml(-1)) to the C8161 cells at an effector:tumour cell ratio of 40:1 caused a 2.3-fold reduction in lysis of tumour cells and a 3-fold reduction in lysis of RA-treated cells. Blocking ICAM-1 antibody at optimum concentrations of 5 microg ml(-1) reduced lysis 1.8-fold in control Hs294T cells and 1.3-fold in RA-treated cells. Blocking the HLA-ABC complex had no effect on lysis. The more highly metastatic 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 assay failed to affect lysis of either cell line but did induce a 2-fold decrease in lysis of RA-treated C8161 cells. Collectively, these data provide further evidence for ICAM-1 involvement in the tumour/LAK cell response and indicates that the RA-induced increase in mICAM-1 levels are partly responsible 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.
Alexander
C L
CL
Department of Dermatology, University of Glasgow, UK.
Edward
M
M
MacKie
R M
RM
D000906:Antibodies / Q000276:immunology; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D018799:Intercellular Adhesion Molecule-1; D014212:Tretinoin