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      Expression of CD40 and CD40L in Gastric Cancer Tissue and Its Clinical Significance

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          Abstract

          To study expression of CD40 and CD40L in gastric cancer tissue we assessed gastric cancer patients admitted to the Department of Gastroenterology of The First Affiliated Hospital of Soochow University and control subjects. Gastric cancer and normal (from around tumours) tissue samples were obtained from patients. Venous blood samples (gastric cancer and ulcer groups) were drawn on the morning of the day before surgery for the measurement of peripheral sCD40L. The expression of CD40 in gastric carcinoma specimens was examined immuno-histochemically. The clinicopathological factors, including age, sex, tumor size, gross appearance, degree of cellular differentiation, histological classification, depth of tumor invasion, lymph node metastasis, peritoneal dissemination, and TNM stage were analyzed according to the different expression of CD40. The results indicated a high CD40 expression in gastric cancer tissues. This positive expression of CD40 revealed a significant (P < 0.05) correlation with lymphatic metastasis and tumor TNM stage in gastric cancer patients. It is concluded that higher CD40 expression existed in expanding type tumors and could play an important role in clinical diagnosis of gastric cancer patients.

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          CD40-CD40 ligand.

          Edwin van den Oord, J Banchereau (1999)
          CD40 is a cell surface receptor that belongs to the tumor necrosis factor-R (TNF-R) family, and that was first identified and functionally characterized on B lymphocytes. Its critical role in T cell-dependent humoral immune responses was demonstrated by patients with the hyper-IgM syndrome, as well as by gene targeting in mice. However, in recent years it has become clear that CD40 is expressed much more broadly, including expression on monocytes, dendritic cells, endothelial cells, and epithelial cells. In addition, the CD40-ligand (CD40-L/CD154), a member of the TNF family, is also expressed more widely than activated CD4+ T cells only. Therefore it is now thought that CD40-CD40-L interactions play a more general role in immune regulation. Collectively these studies have culminated in pre-clinical and clinical studies that are in progress. This article reviews recent developments in this field of research, with main emphasis on (1) structure and expression of CD40 and its ligand; (2) CD40 signal transduction; (3) in vitro function of CD40 on different cell types; and (4) in vivo functions of CD40/CD40-L interactions.
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            Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina. Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes.

            P Aukrust, L Gullestad, E Aaser … (1999)
            The CD40 ligand (CD40L) on activated T cells and platelets may be activating matrix metalloproteinases, inducing procoagulant activity, and be involved in the pathogenesis of acute coronary syndromes by promoting plaque rupture in atheroma. To study the role of CD40L-CD40 interaction in coronary disease, we analyzed levels of soluble (s) and membrane-bound CD40L in the peripheral blood from 29 patients with stable angina, 26 with unstable angina, and 19 controls. Our main findings follow. (1) Patients with unstable angina had significantly raised serum levels of sCD40L when compared with patients with stable angina and controls. (2) Platelets could release large amounts of sCD40L when stimulated ex vivo with the thrombin receptor-agonist peptide SFLLRN in both patients and controls. (3) Platelets in patients with unstable angina were characterized ex vivo by decreased intracellular levels and decreased SFLLRN-stimulated release of sCD40L, which may possibly represent a higher percentage of degranulated platelets in these patients. (4) T cells in patients with unstable angina had enhanced surface expression of CD40L and increased release of sCD40L on anti-CD3/anti-CD28 stimulation in vitro when compared with patients with stable angina and controls. (5) Recombinant CD40L and serum from patients with unstable angina who had high sCD40L levels induced enhanced release of monocyte chemoattractant peptide-1 from mononuclear cells, a CC-chemokine involved in the pathogenesis of atherosclerosis. This first demonstration of enhanced levels of soluble and membrane-bound forms of CD40L in angina patients, with particularly high levels in patients with unstable angina, suggests that CD40L-CD40 interaction may play a pathogenic role in both the long-term atherosclerotic process and in the triggering and propagation of acute coronary syndromes.
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              Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM.

              L. Notarangelo, David Etzioni, Philip Hayward … (1997)
              We report an association between X-linked immunodeficiency with hyper-IgM (XHIM) and carcinomas affecting the liver, pancreas, biliary tree, and associated neuroectodermal endocrine cells. The tumors were fatal in eight of nine cases and in most instances were preceded by chronic cholangiopathy and/or cirrhosis. An additional group of subjects with XHIM had chronic inflammation of the liver or bile ducts but no malignancy. Many patients with XHIM were infected with cryptosporidia. CD40 is normally expressed on regenerating or inflammed bile duct epithelium. A CD40+ hepatocellular carcinoma cell line, HepG2, susceptible to cryptosporidia and CMV infection became resistant when cell surface CD40 was cross-linked by a CD40 ligand fusion protein. Apoptosis was triggered in HepG2 cells if protein synthesis was blocked by cycloheximide or if the cells were infected by cryptosporidia. Ligation of CD40 on biliary epithelium may contribute to defense against infection by intracellular pathogens. We propose that the CD40 ligand mutations that cause XHIM deprive the biliary epithelium of one line of defense against intracellular pathogens and that malignant transformation in the biliary tree follows chronic infection or inflammation. The resulting tumors may then progress without check by an effective immune response. Patients with XHIM who have abnormal liver function tests should be considered at increased risk for cholangiopathy or malignancy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: Molecular Diversity Preservation International (MDPI)
                ISSN (Electronic): 1422-0067
                Publication date Collection: September 2009
                Publication date (Electronic): 4 September 2009
                Volume: 10
                Issue: 9
                Pages: 3900-3917
                Affiliations
                [1 ] Department of Gastroenterology, First Affiliated Hospital of Soochow University; Key Laboratory of Medicine and Clinical Immunology of Jiangsu Province, Suzhou 215006, China; E-Mail: liruidoc@ 123456gmail.com (R.L.)
                [2 ] Department of Emergency, Second Affiliated Hospital of Soochow University, Suzhou 215004, China
                [3 ] Institute of Medical Biotechnology, Soochow University, Suzhou 215007, China
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: chenwcdoc@ 123456gmail.com (W.-C.C.); Tel. +86-512-65223637; Fax: +86-512-65228072.
                Article
                Publisher ID: ijms-10-03900
                DOI: 10.3390/ijms10093900
                PMC ID: 2769148
                PubMed ID: 19865524
                SO-VID: a24505e0-ce48-443a-a97b-3ab2717c08ad
                Copyright © © 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
                License:

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 30 July 2009
                Date revision received : 18 August 2009
                Date accepted : 2 September 2009
                Categories
                Subject: Article

                ScienceOpen disciplines: Molecular biology
                Keywords: cd40,cd40l,gastric cancer,apoptosis,cd138
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: cd40, cd40l, gastric cancer, apoptosis, cd138

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