ICAM‐1 expression and the soluble ICAM‐1 level for evaluating the metastatic potential of gastric cancer

Abstract

ICAM-1 plays an important role in cell-cell and cell-extracellular matrix interactions, especially tumor invasion and cytotoxicity of lymphocytes. In the present study, the relationship between metastasis of gastric cancer and ICAM-1 expression by cancer cells or the serum level of s-ICAM-1 was (s-ICAM-1) was examined. ICAM-1 was detected by immunohistochemic staining in 49.0% of 108 patients with gastric cancer. The ICAM-1 expression rate was higher at a more advanced stage, based on lymph node metastasis, being 46.9% in node-negative and 56.1% in node-positive cases. In patients with liver metastasis, the rate was 90.9%, while it was 43.3% in patients without liver metastasis (p < 0.05). The serum s-ICAM-1 level was 262.1 ng/ml (median 205.5, range 176.0-271.0) in healthy subjects and 391.5 ng/ml (median 317.5, range 148.7-1,768.0) in gastric cancer patients (p < 0.001). The serum s-ICAM-1 level was significantly higher in patients with liver metastasis than in patients without liver metastasis (p < 0.0001). In addition, positive ICAM-1 expression cases had significantly higher s-ICAM-1 levels than negative ones, 408.9 ؎ 188.4 and 308. Cell adhesion molecules have been examined as substances involved in cell-cell adhesion, adhesion between cells and the extracellular matrix and cellular interactions such as the immune response; and their structure and function have been gradually clarified. ICAM-1 1,2 and ICAM-2 3 are cell adhesion molecules identified as ligands of LFA-1, 4 which is expressed by lymphocytes; they are expressed by various cells such as vascular endothelial cells, fibroblasts and epithelial cells. 5 ICAM-1 is a glycoprotein with an extracellular region that has an immunoglobulinlike structure and it belongs to the immunoglobulin superfamily. 6,7 Its expression is enhanced by cytokines such as IL-1 and IFN-␥. 5 ICAM-1 has at least 2 integrin receptors 7 as ligands, LFA-1 (CD11a/CD18) and MAC-1 (CD11b/CD18). 8,9 Migration of granulocytes from blood vessels is mediated by adhesion between ICAM-1 and LFA-1 8,10 and ICAM-1 is also involved in adhesion to target cells before destruction by killer cells (NK cells, LAK cells and CTLs); 11,12 thus, it is important for the local immune response. The activity of LAK and NK cells is suppressed by administration of anti-ICAM-1 antibody. 13-15 s-ICAM-1 has been reported in serum 16 -18 and quantified by ELISA. Like the membrane-bound form of ICAM-1, s-ICAM-1 also has 5 domains, suppresses the adhesion of T cells by binding to LFA-1 16 and inhibits NK and LAK cell activity. 14,18 There are several distinct steps in the process of tumor cell metastasis, including detachment of cancer cells from the primary lesion, penetration through the tissue basement membrane, invasion of blood vessels and migration to the target organ. 19 Cancer cells with a high metastatic potential have properties that facilitate each step of metastasis. Concerning the detachment of cancer cells, an increase in metastatic potential has been reported 20,21 along with reduction of cadheri...

Subtractive immunization using highly metastatic human tumor cells identifies SIMA135/CDCP1, a 135 kDa cell surface phosphorylated glycoprotein antigen

“…The distinct loss of glandular tissue ultrastructure that is apparent during tumorigenesis may permit the release of the soluble form of SIMA135/ CDCP1 into the fluid and vascular system of the colon cancer patient. Accordingly, although there may not be a major difference in SIMA135/CDCP1 protein expression level in normal and cancerous colon, this protein might have utility as a serum or tissue fluid marker as has been proposed for the transmembrane proteins MUC1 (Rye and McGuckin, 2001), CD44 (Adham et al, 1990) and ICAM-1 (Maruo et al, 2002). Additional experiments are necessary to determine whether SIMA135/CDCP1 has a functional role in malignant progression and whether a released form of this protein is present at elevated levels in cancer patient fluids.…”

Molecular background of the regional lymph node metastasis of gastric cancer (Review)

“…Yashiro et al (60) suggested that ICAM-1 facilitates GC cell adhesion to immune cells, leading to immune tolerance (Table II). However, other studies have demonstrated an association between the serum levels of circulating ICAM-1 and GC tumor progression, with higher levels indicating a worse prognosis (53,61,62). On account of the contradictory results in these studies, ICAM-1 has not yet been established as a prognostic marker in GC.…”

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

“…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). By contrast, Yashiro et al reported that decreased CD54 expression on cancer cells was significantly correlated with lymphatic spread, which suggested that decreased CD54 might be associated with decreased cytotoxity of immune cells (21).…”