Group Of Cell Adhesion Molecules Research Articles

Cross-Talk between the TGF-β and Cell Adhesion Signaling Pathways in Cancer.

Transforming growth factor-β (TGF-β) is strongly associated with the cell adhesion signaling pathway in cell differentiation, migration, etc. Mechanistically, TGF-β is secreted in an inactive form and localizes to the extracellular matrix (ECM) via the latent TGF-β binding protein (LTBP). However, it is the release of mature TGF-β that is essential for the activation of the TGF-β signaling pathway. This progress requires specific integrins (one of the main groups of cell adhesion molecules (CAMs)) to recognize and activate the dormant TGF-β. In addition, TGF-β regulates cell adhesion ability through modulating CAMs expression. The aberrant activation of the TGF-β signaling pathway, caused by abnormal expression of key regulatory molecules (such as Smad proteins, certain transcription factors, and non-coding RNAs), promotes tumor invasive and metastasis ability via epithelial-mesenchymal transition (EMT) during the late stages of tumorigenesis. In this paper, we summarize the crosstalk between TGF-β and cell adhesion signaling pathway in cancer and its underlying molecular mechanisms.

Nectins and Nectin-like molecules drive vascular development and barrier function.

Angiogenesis, barriergenesis, and immune cell migration are all key physiological events that are dependent on the functional characteristics of the vascular endothelium. The protein family of Nectins and Nectin-like molecules (Necls) is a group of cell adhesion molecules that are widely expressed by different endothelial cell types. The family includes four Nectins (Nectin-1 to -4) and five Necls (Necl-1 to -5) that either interact with each other by forming homo- and heterotypical interactions or bind to ligands expressed within the immune system. Nectin and Necl proteins are mainly described to play a role in cancer immunology and in the development of the nervous system. However, Nectins and Necls are underestimated players in the formation of blood vessels, their barrier properties, and in guiding transendothelial migration of leukocytes. This review summarizes their role in supporting the endothelial barrier through their function in angiogenesis, cell-cell junction formation, and immune cell migration. In addition, this review provides a detailed overview of the expression patterns of Nectins and Necls in the vascular endothelium.

Integrins: An Important Link between Angiogenesis, Inflammation and Eye Diseases.

Integrins belong to a group of cell adhesion molecules (CAMs) which is a large group of membrane-bound proteins. They are responsible for cell attachment to the extracellular matrix (ECM) and signal transduction from the ECM to the cells. Integrins take part in many other biological activities, such as extravasation, cell-to-cell adhesion, migration, cytokine activation and release, and act as receptors for some viruses, including severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). They play a pivotal role in cell proliferation, migration, apoptosis, tissue repair and are involved in the processes that are crucial to infection, inflammation and angiogenesis. Integrins have an important part in normal development and tissue homeostasis, and also in the development of pathological processes in the eye. This review presents the available evidence from human and animal research into integrin structure, classification, function and their role in inflammation, infection and angiogenesis in ocular diseases. Integrin receptors and ligands are clinically interesting and may be promising as new therapeutic targets in the treatment of some eye disorders.

Adhesion Molecules in Non-melanoma Skin Cancers: A Comprehensive Review.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequently diagnosed cancers, generating significant medical and financial problems. Cutaneous carcinogenesis is a very complex process characterized by genetic and molecular alterations, and mediated by various proteins and pathways. Cell adhesion molecules (CAMs) are transmembrane proteins responsible for cell-to-cell and cell-to-extracellular matrix adhesion, engaged in all steps of tumor progression. Based on their structures they are divided into five major groups: cadherins, integrins, selectins, immunoglobulins and CD44 family. Cadherins, integrins and CD44 are the most studied in the context of non-melanoma skin cancers. The differences in expression of adhesion molecules may be related to the invasiveness of these tumors, through the loss of tissue integrity, neovascularization and alterations in intercellular signaling processes. In this article, each group of CAMs is briefly described and the present knowledge on their role in the development of non-melanoma skin cancers is summarized.

Contactins in the central nervous system: role in health and disease.

Contactins are a group of cell adhesion molecules that are mainly expressed in the brain and play pivotal roles in the organization of axonal domains, axonal guidance, neuritogenesis, neuronal development, synapse formation and plasticity, axo-glia interactions and neural regeneration. Contactins comprise a family of six members. Their absence leads to malformed axons and impaired nerve conduction. Contactin mediated protein complex formation is critical for the organization of the axon in early central nervous system development. Mutations and differential expression of contactins have been identified in neuro-developmental or neurological disorders. Taken together, contactins are extensively studied in the context of nervous system development. This review summarizes the physiological roles of all six members of the Contactin family in neurodevelopment as well as their involvement in neurological/neurodevelopmental disorders.

A crossroad of neuronal diversity to build circuitry.

Clustered protocadherin genes control convergence and divergence of neurons

Cell Adhesion Molecules and Ubiquitination-Functions and Significance.

Cell adhesion molecules of the immunoglobulin (Ig) superfamily represent the biggest group of cell adhesion molecules. They have been analyzed since approximately 40 years ago and most of them have been shown to play a role in tumor progression and in the nervous system. All members of the Ig superfamily are intensively posttranslationally modified. However, many aspects of their cellular functions are not yet known. Since a few years ago it is known that some of the Ig superfamily members are modified by ubiquitin. Ubiquitination has classically been described as a proteasomal degradation signal but during the last years it became obvious that it can regulate many other processes including internalization of cell surface molecules and lysosomal sorting. The purpose of this review is to summarize the current knowledge about the ubiquitination of cell adhesion molecules of the Ig superfamily and to discuss its potential physiological roles in tumorigenesis and in the nervous system.

239 MOLECULAR MECHANISMS OF SPECIFIC INHIBITION OF RENAL CELL CANCER (RCC) CELL MIGRATION BY THE DISINTEGRIN ECHISTATIN

You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011239 MOLECULAR MECHANISMS OF SPECIFIC INHIBITION OF RENAL CELL CANCER (RCC) CELL MIGRATION BY THE DISINTEGRIN ECHISTATIN Wolfgang Jäger, Frederik Roos, Anna Becker, Elke Schneider, Joachim Thüroff, Christian Hampel, and Walburgis Brenner Wolfgang JägerWolfgang Jäger Mainz, Germany More articles by this author , Frederik RoosFrederik Roos Mainz, Germany More articles by this author , Anna BeckerAnna Becker Mainz, Germany More articles by this author , Elke SchneiderElke Schneider Mainz, Germany More articles by this author , Joachim ThüroffJoachim Thüroff Mainz, Germany More articles by this author , Christian HampelChristian Hampel Mainz, Germany More articles by this author , and Walburgis BrennerWalburgis Brenner Mainz, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.308AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metastasis depends on adhesion of tumor cells to the endothelium, migration into subendothelial tissue and proliferation in secondary organs. Particularly during cell migration, binding of integrins, a group of cell adhesion molecules, to extracellular matrix is mediated by the amino acid sequence arginine-glycine-aspartate (RGD). Disintegrins, RGD containing proteins, can block integrins and thus inhibit cell migration and possibly metastasis. We analyzed the influence of disintegrins kistrin and echistatin on the migration of RCC cells. METHODS RCC-RC1 cells were pre-incubated with kistrin, echistatin and RGD containing peptides (P-RGD-M analogue to kistrin, A-RGD-D analogue to echistatin, G-RGD-S analogue to fibronectin, and RGD tripeptide). Migration was subsequently quantified in a boyden chemotaxis chamber. To analyse the binding mechanisms of these molecules, maleic anhydride activated plates (Pierce) were coated with echistatin, kistrin and the RGD containing molecules and the adherence of tumor cells, pre-incubated with á5- and 1-integrin-blocking antibodies, was quantified. The importance of the tertiary structure of the disintegrins was analysed by previous splitting of the disulfide chains. RESULTS In contrast to kistrin, echistatin significantly reduces tumor cell migration. Of the RGD containing peptides, G-RGD-S inhibited cell migration up to 45% and A-RGD-D up to 80%, whereas P-RGD-M did not show any inhibitory influence. Tumor cell adhesion was equally strong in echistatin and kistrin, and to a lower extent in fibronectin, but there was only a very weak binding to other RGD containing peptides. Previous incubation of RCC cells with integrin-blocking antibodies did not have any influence on tumor cell adhesion either. After splitting the disulfide chains of the disintegrins, the inhibitory effect of echistatin on tumor cell migration was reversed. Tumor cells also showed no adhesion to the modified echistatin. CONCLUSIONS Both disintegrins, echistatin and kistrin, contain the amino acid sequence RGD in equal amounts. After incubating RCC cells with disintegrins, only echistatin inhibited tumor cell migration. This effect seems not to be caused by a different binding capacity of these agents. After splitting the disulfide chains of echistatin and consequently destructing its proper tertiary structure, tumor cells lost adhesion capability. Subsequently inhibition of cell migration was not possible. Therefore a proper placement of the amino acid sequence RGD in echistatin is crucial for its inhibitory effects. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e97 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wolfgang Jäger Mainz, Germany More articles by this author Frederik Roos Mainz, Germany More articles by this author Anna Becker Mainz, Germany More articles by this author Elke Schneider Mainz, Germany More articles by this author Joachim Thüroff Mainz, Germany More articles by this author Christian Hampel Mainz, Germany More articles by this author Walburgis Brenner Mainz, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Losac, the First Hemolin that Exhibits Procogulant Activity through Selective Factor X Proteolytic Activation

Envenoming by the contact of human skin with Lonomia obliqua caterpillars promotes a hemorrhagic syndrome characterized by a consumptive coagulopathy. Losac (Lonomia obliqua Stuart factor activator) is a component of the bristle of L. obliqua that is probably partially responsible for the observed syndrome because it activates factor X and is recognized by an effective antilonomic serum. Here we unveil the proteolytic activity of Losac and demonstrate the feasibility of its recombinant production. On the other hand, Losac has no homology to known proteases, but it can be inhibited by PMSF, a serine protease inhibitor. Instead, it shows closer homology to members of the hemolin family of proteins, a group of cell adhesion molecules. The recombinant protein (rLosac) shortened the coagulation time of normal and deficient plasmas, whereas it was ineffective in factor X-deficient plasma unless reconstituted with this protein. rLosac was able to activate factor X in a dose- and time-dependent manner but not γ-carboxyglutamic acid domainless factor X. Moreover, phospholipids and calcium ions increased rLosac activity. Also, rLosac had no effect on fibrin or fibrinogen, indicating its specificity for blood coagulation activation. Linear double reciprocal plots indicate that rLosac follows a Michaelis-Menten kinetics. Cleavage of factor X by rLosac resulted in fragments that are compatible with those generated by RVV-X (a well known factor X activator). Together, our results validate Losac as the first protein from the hemolin family exhibiting procoagulant activity through selective proteolysis on coagulation factor X.

Nodes of Ranvier Act as Barriers to Restrict Invasion of Flanking Paranodal Domains in Myelinated Axons

Accumulation of voltage-gated sodium (Na(v)) channels at nodes of Ranvier is paramount for action potential propagation along myelinated fibers, yet the mechanisms governing nodal development, organization, and stabilization remain unresolved. Here, we report that genetic ablation of the neuron-specific isoform of Neurofascin (Nfasc(NF¹⁸⁶)) in vivo results in nodal disorganization, including loss of Na(v) channel and ankyrin-G (AnkG) enrichment at nodes in the peripheral nervous system (PNS) and central nervous system (CNS). Interestingly, the presence of paranodal domains failed to rescue nodal organization in the PNS and the CNS. Most importantly, using ultrastructural analysis, we demonstrate that the paranodal domains invade the nodal space in Nfasc(NF¹⁸⁶) mutant axons and occlude node formation. Our results suggest that Nfasc(NF¹⁸⁶)-dependent assembly of the nodal complex acts as a molecular boundary to restrict the movement of flanking paranodal domains into the nodal area, thereby facilitating the stereotypic axonal domain organization and saltatory conduction along myelinated axons.

Stress-induced changes in the expression of monocytic β2-integrins: The impact of arousal of negative affect and adrenergic responses to the Anger Recall Interview

Adhesion of circulating monocytes to the vascular endothelium is one of the earliest steps in the development of atherosclerosis. This leukocyte-to-endothelium interaction is mediated in part by β2-integrins, a group of cell adhesion molecules that bind to endothelial ligands. Given the significance of this interaction to atherogenesis, we examined the effects of stress, operationalized as the arousal of negative affect (NA) and cardiovascular and catecholamine responses to the Anger Recall Interview (ARI), on the expression of LFA-1 (CD11a), Mac-1 (CD11b) and p150/95 (CD11c) on circulating monocytes (CD14+). Subjects were 173 healthy, nonsmoking men and women (60% men, 40% minorities, aged 18–49 year). Arousal of NA, cardiovascular responses (heart rate [HR], systolic blood pressure [SBP], diastolic blood pressure [DBP]), circulating catecholamines (epinephrine [Epi], norepinephrine [Ne]) and β2-integrin (CD11/CD18) expression were determined prior to and following the ARI. The principal findings were that the ARI, on average, induced a decrease in monocyte expression of β2-integrins. However, after adjusting for age, sex, body mass index, exercise status, and baseline level of β2-integrin expression, those individuals who showed the largest increases in NA, Ne and DBP during the ARI showed an increase in monocyte β2-integrin expression. Thus, heightened psychological and physiological stress responses induced phenotypic changes in monocytic expression of β2-integrins that are consistent with the role of monocytes/macrophages in vascular inflammation and increased risk of atherosclerotic cardiovascular disease.

Recombinant P-selectin glycoprotein ligand–immunoglobulin, a P-selectin antagonist, as an adjunct to thrombolysis in acute myocardial infarction. The P-Selectin Antagonist Limiting Myonecrosis (PSALM) trial

Inflammatory responses induced by reperfusion of previously ischemic myocardial tissue may lead to further damage of the microvascular structures. A group of cell adhesion molecules, named selectins, initiate those inflammatory changes at the endothelial wall surface. Recombinant P-selectin glycoprotein ligand-immunoglobulin (rPSGL-Ig), a P-selectin antagonist, was shown to have beneficial effects in several animal models of acute myocardial ischemia. We performed a mechanistic study with positron emission tomography to test the potential benefits of rPSGL-Ig in patients with ST-segment elevation acute myocardial infarction. Patients with ST-elevation acute myocardial infarction presenting within the first 6 hours of onset of chest pain were enrolled. All patients received alteplase. Patients were randomly assigned in a 1:1:1 ratio to 3 treatment groups: placebo; 75 mg rPSGL-Ig; 150 mg rPSGL-Ig, given intravenously. Coronary angiography was performed 90 minutes after the start of thrombolytic therapy for TIMI flow grading. Myocardial blood flow (MBF) was measured with 13NH3 at rest and after adenosine administration on day 5. Myocardial blood flow at rest was measured again at day 30, followed by measurement of 18FDG uptake. In addition, a multigated acquisition, gated equilibrium blood pool study was performed at day 30. Continuous 12-lead electrocardiogram recording was performed during the first 24 hours. The trial was prematurely stopped by the sponsor for lack of efficacy in an accompanying larger trial after enrolling 88 patients in the current study. Median MBF in the infarct-related territory (expressed as percentage of the normalized blood flow) at day 5 was similar in the 3 treatment groups (9.1% in the placebo group vs 3.8% in the 75-mg dose and 4.3% in the 150-mg rPSGL-Ig treatment group; P = not significant). No significant differences in MBF reserve, myocardial metabolism, ST-segment resolution, left ventricular ejection fraction, or TIMI flow grade were found among the 3 groups. In this prematurely stopped mechanistic study, there was no evidence of a benefit of rPSGL-Ig given as an adjunct to thrombolysis on epicardial vessel patency, myocardial tissue reperfusion, or recovery of function.

Downregulation of vascular endothelial growth factor and integrinβ 3 by endostatin in a mouse model of retinal neovascularization

Retinal neovascularization is among the leading causes of vision impairment throughout the world. Intraocular expression of vascular endothelial growth factor (VEGF), an angiogenic protein, and integrins, a group of cell adhesion molecules, is closely correlated with neovascularization in such neovascular diseases. The purpose of this study is to determine the effect of endostatin, a potent anti-angiogenic factor, on gene expression of vascular endothelial growth factor (VEGF) and integrinβ 3 in a mouse model of oxygen-induced retinopathy. C57BL/6 mice were given intravitreous injections of 1.0 μg endostatin at P 12. At P 17, retinal VEGF and integrinβ 3 mRNA levels were measured by real-time quantitative PCR in the hyperoxia mice and in the endostatin-treated mice. Analysis of 12 separate experiments revealed a 3.5-fold decrease in VEGF levels between hyperoxia mice and endostatin-treated mice ( p<0.01) and a 2.5-fold decrease in integrinβ 3 levels between hyperoxia mice and endostatin-treated mice ( p<0.01). These data suggest that intraocular expression of VEGF and integrinβ 3 mRNA is down-regulated by endostatin, which may provide a new therapeutic approach for ocular neovascularization.

Expression of nectin-2 in mouse granulosa cells

Objective: The development and maturation of the ovarian follicles are characterized by structural changes that require components involved in cell–cell adhesion systems. Recently a novel group of cell adhesion molecules named nectins has been identified. The present study examined expression and cell-specific localization of nectins during mouse follicular development. Study design: Expression of nectins in mouse ovary was investigated by immnuoblot analysis and immunohistochemistry. More precise localization was determined by electron microscopy. Results: Immunoblot analysis revealed expression of nectin-2 and nectin-3 but not nectin-1 in ovarian granulosa cells. Immunohistochemistry demonstrated expression of nectin-2 at cell–cell adhesion sites of granulosa cell layer in the primary and preantral follicles. Especially, intense immunoreactivity of nectin-2 accumulated around the zona pellucida. In antral follicles, the intensity of nectin-2 expression on granulosa cells was decreased. By electron microscopy nectin-2 was detected not only on thin extensions of granulosa cells penetrating the zona pellucida, but also on the attachment sites between thin extensions of granulosa cells and oocyte surface. Conclusion: The restricted expression of nectin-2 in the granulosa cells of primary and preantral follicles might reflect some of the molecular changes in cell–cell adhesion during early follicular development.

The C. elegans hmr-1 Gene Can Encode a Neuronal Classic Cadherin Involved in the Regulation of Axon Fasciculation

Nervous system morphogenesis is characterized by extensive interactions between individual axon growth cones and their cellular environments. Selective cell adhesion is one mechanism by which the growth of an axon can be modulated, and members of the classic cadherin group of cell adhesion molecules have been shown to play a role in this process in both vertebrates and Drosophila[1–4]. In Drosophila, there are two classic cadherins: one involved primarily in regulating the morphogenesis of epithelia [5, 6], and the other, DN-cadherin [3], required almost exclusively in neuronal development. In contrast, C. elegans has a single classic cadherin gene, hmr-1, whose function is required for epithelial morphogenesis [7]. We show here that hmr-1 also encodes a second classic cadherin via a novel mechanism involving an alternative, neuron-specific promoter, coupled with alternative splicing. This novel HMR-1 isoform is very similar to DN-cadherin, and a mutant strain that specifically lacks the function of this isoform displays defects in the fasciculation and outgrowth of a subset of motor neuron processes; a phenotype that resembles loss of DN-cadherin function in Drosophila. These results indicate that Drosophila and C. elegans share a conserved, cadherin-dependent mechanism involved in regulating axonal patterning and fasciculation.

Modularity in vertebrate brain development and evolution.

Embryonic modularity and functional modularity are two principles of brain organization. Embryonic modules are histogenetic fields that are specified by position-dependent expression of patterning genes. Within each embryonic module, secondary and higher-level pattern formation takes places during development, finally giving rise to brain nuclei and cortical layers. Defined subsets of these structures become connected by fiber tracts to form the information-processing neural circuits, which represent the functional modules of the brain. We review evidence that a group of cell adhesion molecules, the cadherins, provides an adhesive code for both types of modularity, based on a preferentially homotypic binding mechanism. Embryonic modularity is transformed into functional modularity, in part by translating early-generated positional information into an array of adhesive cues, which regulate the binding of functional neural structures distributed across the embryonic modules. Brain modularity may provide a basis for adaptability in evolution.

A Structure-Function Study of Ligand Recognition by CD22β

B-cell-specific CD22 is a member of a group of cell adhesion molecules within the immunoglobulin superfamily that display binding to glycans with terminal sialic acid residues. Binding of endogenous ligands to CD22 triggers B-cell activation and proliferation. It is therefore conceivable that high affinity ligands for CD22 may be of value as inhibitors of B-cell activation in allergy and chronic inflammation. In this study, we aimed to delineate the structural requirements for ligand binding to CD22. A library of 20 mono-, di-, and trisaccharide analogs of the basic binding motif Neu5Ac(alpha2,6)Lac was synthesized and screened for affinity for CD22beta. In general, CD22 ligand recognition appeared to be rather tolerant with respect to structural modifications of the anomeric sugar on a mono-, di-, and trisaccharide level, although affinity was increased by the presence of a nitro aromatic group at C-2. The most potent monovalent ligand, Neu5Ac-4-nitrobenzoyl-Glc, was selected to generate multivalent ligands based on either a glutamate or Tris cluster core. All multivalent ligands displayed at least a 10-fold increased affinity for CD22 compared with the corresponding monovalent glycoside. Interestingly, a maximal gain in affinity was already obtained for bivalent ligands, regardless of the terminal glycoside. A trivalent Tris-based cluster of Neu5Ac-4-nitrobenzoyl-Glc displayed a 300-fold higher affinity compared with the basic binding motif, which makes it, to our knowledge, the most potent antagonist for CD22 yet synthesized. As our in vitro fluorescence-activated cell sorting studies demonstrated efficient cellular uptake of a CD22 substrate, the most potent ligand in this study may hold promise as a homing device for immunomodulatory compounds and cytostatics.

Soluble endothelial and platelet selectins in serum and ascitic fluid of women with ovarian hyperstimulation syndrome.

The selectins, a group of cell adhesion molecules, are major mediators of inflammatory, immunologic, and angiogenic reactions. Their possible involvement and levels of the soluble isoform in serum and ascitic fluid of women with ovarian hyperstimulation syndrome (OHSS) were not previously evaluated. This prospective, case-control study involved 16 women with OHSS. Ten matched women treated by controlled ovarian stimulation and eight healthy women with normal diagnostic laparoscopy served as controls. Serum and peritoneal fluid samples obtained from all subjects were assayed for soluble endothelial selectin (sES) and soluble platelet selectin (sPS) by specific enzyme-linked immunosorbent assay. Significantly higher levels of sES (median, 17.1 [9-41] vs 9.3 [2.4 21.3] ng/mL [P = 0.03]) and sPS (median, 23 [13-277] vs 6.5 [1.6-28.7] ng/mL [P = 0.001]) were observed in the peritoneal fluid of women with OHSS than the basal levels of healthy, non-stimulated women. Women with OHSS had significantly lower sES serum levels than those treated by controlled ovarian hyperstimulation without OHSS, while their sPS serum levels were comparable. Ascitic fluid of women with OHSS contains appreciable amounts of soluble selectins, suggesting their ovarian origin and possible involvement in the syndrome.

The Role of Epithelial and Vascular-Endothelial Cadherin in the Differentiation and Maintance of Tissue Integrity

The present review has focused on the cell adhesion molecules from the cadherin superfamily, in particular on E- and VE-cadherin. In general, cadherins are a large group of cell adhesion molecules located at intercellular junctions called adherent junctions. They play an important role in embryogenesis and morphogenesis in animals and humans due to their adhesive and cell-signalling functions. Disturbances of the expression or function of cadherins and their associated proteins called catenins are crucial for the initiation and development of many pathological states. E-cadherin is an epithelium-specific cadherin that is required for the development and maintenance of the normal function of all epithelial cells in tissues. The loss or down-regulation of E-cadherin is a key event in the process of tumour invasion and metastasis. The assessment of E-cadherin immunoreactivity may be a useful prognostic marker in some cancers, complementary to the established prognostic factors. VE-cadherin is an endothelium-specific cadherin, which plays a relevant role in vascular homeostasis. It has been demonstrated that VE-cadherin is required for normal vasculogenesis, angiogenesis, and for the maintenance of vascular integrity. Disruption of VE-cadherin-catenin complexes by some inflammatory agents such as thrombin, by inflammatory cells, or shear stress is accompanied by an increase in vascular permeability in vivo and in vitro.

E- and P-selectin expression in endometriotic tissues and the corresponding endometria

Endometriosis is one of the most frequent diseases in gynecology. It is histologically defined as a non-malignant pathology in which endometrial-like tissue is found outside the uterus. The pathogenesis and mechanisms involved in the development of endometriosis-associated pain symptoms are still under investigation. A local peritoneal inflammation seems to play an important role in the origin of these symptoms.Selectins belong to a group of cell adhesion molecules that mediate the localization of circulating leukocytes on the endothelium at the sites of inflammation. The aim of this study was to investigate the expression of E- and P-selectins in endometriotic tissues and the corresponding endometria.Thirty endometriotic samples, 13 corresponding endometria and six endometria of patients without endometriosis were analyzed using an immunohistochemical technique.Just two endometriotic tissues expressed E-selectin, while five samples were positive for P-selectin. The selectin expression of the corresponding endometria was also very weak. No correlations between the revised American Fertility Society (rAFS) score or the hormonal situation of the patients at the time of biopsy and the selectin expression could be found.In conclusion, the selectin expression in endometriotic glands does not play an important role in the initiation of inflammatory processes caused by endometriosis. This inflammation must be considered as a secondary reaction after the implantation of the endometriotic glands, so that endometriotic tissues are not able to induce, by the expression of selectins, a direct inflammation.