Expression and shedding of ICAM-1 in bladder cancer and its immunotherapy.
Intercellular adhesion molecule-1 (ICAM-1) is one of 3 major ligands for the beta 2 integrin leucocyte function-associated antigen-1 (LFA-1). Several reports have emerged describing soluble forms of ICAM-1 in association with normal and pathological states (e.g., malignancy). In this study we have identified the secretion of soluble ICAM-1 in tissue culture supernatants from bladder tumour monolayers and in the urine of patients receiving intravesical BCG immunotherapy for superficial bladder cancer. In vitro, small amounts of sICAM-1 were detected in the tissue culture supernatants of bladder cancer cells, known to constitutively express ICAM-1. Following stimulation with interferon gamma, the levels of sICAM-1 increased inversely to the levels of cell surface ICAM-1, suggesting sheeding. Induction and augmentation of cell surface ICAM-1 required de novo mRNA and protein synthesis. However, treatment with cycloheximide, after stimulation with IFN-gamma, resulted in increased levels of membrane associated ICAM-1. Correspondingly, the level of sICAM-1 in the supernatant was low in comparison with controls, suggesting that cycloheximide acted via stabilization of membrane ICAM-1 or via prevention of some enzymatic cleavage event. In vivo, sICAM-1 can be detected at high levels in patients' urine following immunotherapy of bladder cancer with intravesically administered BCG organisms. Production of sICAM-1 is transient and occurs only in the first 12 hr following installation. Furthermore, production of sICAM-1 is heterogeneous as some patients fail to produce any at all. If the source of sICAM-1 is the bladder tumour per se, then its detection in urine could indicate a response of the tumour to immunotherapy and indeed may prove a useful indicator of clinical response.
Jackson
A M
AM
Department of Surgery (WGH), University of Edinburgh Medical School, UK.
Alexandrov
A B
AB
Gribben
S C
SC
Esuvarnathan
K
K
James
K
K
D001500:BCG Vaccine / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000628:therapy / Q000652:urine; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000652:urine; D003513:Cycloheximide / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000628:therapy / Q000652:urine
D001500:BCG Vaccine; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D003513:Cycloheximide