Adhesion molecules in inflammatory bowel disease.

Jones, Susan; Banks, Rosamonde E.; Haidar, Aqeel; Gearing, A. J. H.; Hemingway, Ian; Ibbotson, Sally H.; Dixon, M. F.; Axon, A. T. R.

doi:10.1136/gut.36.5.724

Cited by 183 publications

(130 citation statements)

References 42 publications

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“…Recently, circulating forms of several adhesion molecules, including E-cadherin, E-selectin, ICAM-1 and VCAM-1, have been described with their concentrations being increased in inflammatory and malignant diseases, e.g. malignant melanoma, gastrointestinal cancer, lymphoma, hepatocellular cancer (Gearing et al, 1992;Banks et al, 1993;Katayama et al, 1994;Jones et al, 1995;Wittig et al, 1996). Although little investigated so far, soluble forms of adhesion molecules have been linked to clinical behaviour of tumours.…”

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confidence: 99%

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer

Velikova

Banks²,

Gearing³

et al. 1998

Br J Cancer

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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...

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confidence: 99%

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer

Velikova

Banks²,

Gearing³

et al. 1998

Br J Cancer

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“…[8] who described how increased expression of MAdCAM-1, but not of VCAM-1 or intercellular adhesion molecule-1(ICAM-1), mediates the lymphocyte-endothelial cell adhesive interaction in a model of chronic colitis induced by transferring CD45RBhigh T-cells to SCID mice. There are indeed several reports indicating that antibodies against other adhesion molecules (ICAM-1 or VCAM-1) attenuate the increased leucocyte adhesion in intestinal venules [7,18,19]. In the case of ICAM-1, however, we have already reported that up-regulated ICAM-1 is not involved in T lymphocyte-endothelial adhesion in the inflamed colon [15].…”

Section: Discussionmentioning

confidence: 73%

“…We have also demonstrated the functional importance of elevated MAdCAM-1 levels in different animal models of colitis after immunoneutralization of MAdCAM-1 [4,5]. Although other adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) are up-regulated in the intestinal mucosa during inflammatory bowel diseases [3,6,7], the possible involvement of VCAM-1 in lymphocyte recruitment to the inflamed gut is still controversial [4,8]. The relative functional importance of MAdCAM-1 and VCAM-1 in altered lymphocyte trafficking should thus be elucidated.…”

Section: Introductionmentioning

confidence: 88%

Increased lymphocyte trafficking to colonic microvessels is dependent on MAdCAM-1 and C-C chemokine mLARC/CCL20 in DSS-induced mice colitis

Teramoto

Miura

Tsuzuki

et al. 2005

Clinical and Experimental Immunology

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SummaryAlthough enhanced lymphocyte trafficking is associated with colitis formation, little information about its regulation is available. The aim of this study was to examine how the murine liver and activation-regulated chemokine (mLARC/CCL20) contributes to lymphocyte recruitment in concert with vascular adhesion molecules in murine chronic experimental colitis. T and B lymphocytes isolated from the spleen were fluorescence-labelled and administered to recipient mice. Lymphocyte adhesion to microvessels of the colonic mucosa and submucosa was observed with an intravital microscope. To induce colitis, the mice received two cycles of treatment with 2% dextran sodium sulphate (DSS). In some of the experiments antibodies against the adhesion molecules or anti-mLARC/CCL20 were administered, or CC chemokine receptor 6 (CCR6) of the lymphocytes was desensitized with excess amounts of mLARC/CCL20. Significant increases in T and B cell adhesion to the microvessels of the DSS-treated mucosa and submucosa were observed. In chronic colitis, the accumulation of lymphocytes was significantly inhibited by anti-mucosal addressin cell adhesion molecule (MAdCAM)-1 mAb, but not by anti-vascular cell adhesion molecule-1. In DSS-treated colonic tissue, the expression of mLARC/CCL20 was significantly increased, the blocking of mLARC/CCL20 by monoclonal antibody or the desensitization of CCR6 with mLARC/CCL20 significantly attenuated the DSS-induced T and B cell accumulation. However, the combination of blocking CCR6 with MAdCAM-1 did not further inhibit these accumulations. These results suggest that in chronic DSS-induced colitis, both MAdCAM-1 and mLARC/CCL20 may play important roles in T and B lymphocyte adhesion in the inflamed colon under flow conditions.

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“…Osteopontin and tumor necrosis factor receptor signaling (TNFRS) F14 are genes associated with fibrosis/cell adhesion molecules [1,13]. Blockade of these cell adhesion molecule interactions prevents the trafficking of leukocytes across the vascular endothelium and, subsequently, into the parenchymal tissue [14][15][16]. Alpha-4 integrins bind additional ligands in tissues, including OPN and epitopes of fibronectin.…”

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confidence: 99%

Osteopontin Biomarker in Inflammatory Bowel Disease, Animal Models and Target for Drug Discovery

Neuman

2012

Dig Dis Sci

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Adhesion molecules in inflammatory bowel disease.

Abstract: The ability of leucocytes

Cited by 183 publications

References 42 publications

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer

Increased lymphocyte trafficking to colonic microvessels is dependent on MAdCAM-1 and C-C chemokine mLARC/CCL20 in DSS-induced mice colitis

Osteopontin Biomarker in Inflammatory Bowel Disease, Animal Models and Target for Drug Discovery

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