Serum concentrations of soluble adhesion molecules in patients with colorectal cancer

Abstract

Summary The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence. and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 wiare significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.Keywords: E-cadherin; E-selectin; intercellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1); adhesion molecule; colorectal cancer Cellular adhesion molecules play an important role in the process of metastasis. Positive and negative regulation of cell adhesion will influence the process as metastatic cells break away from the primary tumour, travel in the circulation and then adhere to cellular and extracellular matrix elements in particular secondary sites. Several families of cell adhesion molecules have been identified together with specific aberrations in malignant diseases (Zetter, 1993). The cadherins, Ca++-dependent homotypic cell-cell adhesion molecules, are essential for establishing and maintaining intercellular connections. Epithelial cadherin (E-cadherin) plays a crucial role in maintaining the integrity of epithelial tissues and has been positively correlated with tumour differentiation and negatively with infiltrative tumour growth and metastatic potential in a range of cancer types (Takeichi, 1993;Shino et al, 1995). Selectins are transmembrane glycoproteins that mediate heterotypic cell-cell contact through Ca+-dependent interactions with cell surface carbohydrates. In addition to mediating leucocyte adhesion to activated vascular endothelium, endothelial selectin (E-selectin) has been shown to be involved in the adhesion of cancer cells to the vasculature. Stronger adhesion to the endothelium is mediated through other classes of adhesion molecules, namely the integrins and cytokine-inducible endothelial cell adhesion molecules of the immunoglobuli...

Assessment of a fragment of e-cadherin as a serum biomarker with predictive value for prostate cancer

“…It was stated that a high concentration in gastric cancer patients predicted palliative treatment as there was a strong association to metastatic disease (Chan et al, 2001). Although colon cancer is an intestinal neoplasia as well, Velikova et al (1998) could not confirm these findings for colon cancer.…”

“…Association of the 80 kDa expression with clinical and pathological parameters As the 80 kDa fragment has been found to be associated with aggressive clinical course in bladder, gastric and colorectal cancer (Griffiths et al, 1996;Gofuku et al, 1998;Velikova et al, 1998), we looked for potential associations between clinical or pathological parameters in prostate cancer. Two statistical approaches were tested: first step was to create four categories of the 80 kDa serum concentration according to the calculated quartiles; second step was to categorise using the median of the 80 kDa concentration of the cohort of Loc PCA patients.…”

“…In a recent study, an 80 kDa fragment of full-length e-cadherin has been described as almost exclusively being observed in the neoplastic aspect of prostate cancer tissue (Kuefer et al, 2003). This soluble fragment has also been reported as being measurable in the serum of patients suffering from different types of adenocarcinoma (Katayama et al, 1994a;Banks et al, 1995;Gofuku et al, 1998;Velikova et al, 1998;Protheroe et al, 1999;Chan et al, 2003). In the current study, we report the accumulation of this 80 kDa fragment of e-cadherin in the serum of patients affected by prostate cancer.…”

Targeting selectins and selectin ligands in inflammation and cancer

“…Similarly, soluble E-selectin is a chemotactic signal for T84 cells [200]. Several clinical studies have suggested that soluble levels of E-selectin in the serum of subjects with various cancers reflect tumor progression [242][243][244][245][246][247][248], whereas other studies have found no correlation [249][250][251]. In any case, the study of how E-selectin promotes tumor cell extravasation merits additional study.…”

Assessment of Vitronectin, Soluble Epithelial-Cadherin and TGF-β1 as a Serum Biomarker with Predictive Value for Endometrial and Ovarian Cancers

“…Shirahama et al 32 indicated that the levels of serum sEcadherin did not vary significantly from controls in basal cell carcinoma. In colorectal patients, Velikova et al 33 determined that there was no statistically significant difference between sE-cadherin levels between controls and patients. However, Bonaldi et al 17 suggested that sE-cadherin was lower in patients with prostate cancer compared to controls.…”