Expression and shedding of ICAM‐1 in bladder cancer and its immunotherapy

Abstract

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.

Secretion of immunoregulatory cytokines by mesenchymal stem cells

“…Elevated amounts of a biologically active form of sI-CAM is detected in serum, cerebrospinal fluid, synovial fluid, urine and sputum in pathologies with an underlying inflammatory status, like autoimmune and degenerative diseases [213][214][215] and tumor pathogenesis [216,217] . Different reports point to various cell sources of sICAM in health and pathologies, including endothelial cells [218] , peripheral blood mononuclear cells, keratinocytes, epidermoid carcinoma cell lines, melanoma cells [219] and tumors [216,217,220] . sICAM can be secreted spontaneously or after specific inductions [220] .…”

“…Different reports point to various cell sources of sICAM in health and pathologies, including endothelial cells [218] , peripheral blood mononuclear cells, keratinocytes, epidermoid carcinoma cell lines, melanoma cells [219] and tumors [216,217,220] . sICAM can be secreted spontaneously or after specific inductions [220] . Limited data demonstrate that some but not all MSCs are a source of sICAM.…”

CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

“…When CD54 binds to its ligands LFA-1 and Mac-1 on the surface of T lymphocytes, it plays an essential role as a signal transmitter of immune response, which mediates tumor cytotoxicity (17). It has been reported that CD54 expression on the surface of tumor cells increases the susceptibility of such tumor cells to lymphocyte-mediated tumor cytotoxity through the CD54/ LFA-1 system (18,19). Maruo et al suggested that ICAM-1 was overexpressed in cancer cells and released as soluble-ICAM-1, which would promote hematogenous metastasis by suppressing local anticancer immunity (20).…”

ICAM-1 expression by lung cancer cell lines: effects of upregulation by cytokines on the interaction with LAK cells

“…ICAM-1 is constitutively expressed on a variety of inflammatory and immune effector cells and in structural cells, such as: endothelial cells, fibroblasts, and epithelial cells [3]. In addition, ICAM-1 has been detected on the surface of a variety of primary tumours and tumour cell lines, including lymphomas [4], melanomas [5], renal [6], pancreatic [7], bladder [8] and lung carcinomas [9]. Because LFA-1 is expressed on mononuclear phagocytes, cytotoxic T-cells, natural-killer (NK), and lymphokine-activated killer (LAK) cells [1], the expression of ICAM-1 by tumour cells may be involved in the regulation of their susceptibility to cytotoxic activity of autologous and allogeneic defensive cells.…”