Sialyl Lewis x expression in canine malignant mammary tumours: correlation with clinicopathological features and E-Cadherin expression

<p>Abstract</p> <p>Background</p> <p>Sialyl Lewis x (sLe^x) antigen is a carbohydrate antigen that is considered not only a marker for cancer but also implicated functionally in the malignant behaviour of cancer cells. Overexpression of sLe^xis associated with enhanced progression and metastases of many types of cancer including those of the mammary gland. Canine mammary tumours can invade and give rise to metastases via either lymphatic or blood vessels.</p> <p>E-Cadherin is specifically involved in epithelial cell-to-cell adhesion. In cancer, E-Cadherin underexpression is one of the alterations that characterizes the invasive phenotype and is considered an invasion/tumour suppressor gene. Partial or complete loss of E-Cadherin expression correlates with poor prognosis in canine malignant mammary cancer.</p> <p>The aim of this study was to analyse the sLe^xexpression in canine malignant mammary tumours and to evaluate if the presence of sLe^xcorrelates with the expression of E-Cadherin and with clinicopathological features.</p> <p>Methods</p> <p>Fifty-three cases of canine mammary carcinomas were analysed immunohistochemically using monoclonal antibodies against sLe^x(IgM) and E-Cadherin (IgG). The clinicopathological data were then assessed to determine whether there was a correlation with sLe^xtumour expression. Double labelled immunofluorescence staining was performed to analyse the combined expression of sLe^xand E-Cadherin.</p> <p>Results</p> <p>sLe^xexpression was consistently demonstrated in all cases of canine mammary carcinomas with different levels of expression. We found a significant relationship between the levels of sLe^xexpression and the presence of lymph node metastases. We also demonstrated that when E-Cadherin expression was increased sLe^xwas reduced and vice-versa. The combined analysis of both adhesion molecules revealed an inverse relationship.</p> <p>Conclusion</p> <p>In the present study we demonstrate the importance of sLe^xin the malignant phenotype of canine malignant mammary tumours. Our results support the use of sLe^xas a prognostic tumour marker in canine mammary carcinomas. Furthermore, we showed that sLe^xand E-Cadherin expression were inversely correlated. Future studies are warranted to clarify the molecular mechanism underlying the relation between sLe^xand E-Cadherin in canine mammary carcinoma cells which represents an important comparative model to woman breast cancer.</p

Origem coronária anómala: da suspeita à revascularizac¸ão cirúrgica

Congenital anomalies of the coronary arteries are uncommon and can present a diagnostic challenge. The authors present the case of a patient with recurrent chest pain during exertion admitted for acute coronary syndrome. Coronary angiography revealed no coronary lesions but showed that the right coronary artery originated from the anterolateral aortic wall, above the sinuses of Valsalva, leading to suspicion of compression by the pulmonary artery, confirmed by CT angiography. The patient underwent surgical revascularization with a good result. The authors highlight the need to consider compression of an anomalous coronary artery by the pulmonary artery in the differential diagnosis of recurrent chest pain on exertion and acute myocardial infarction without significant coronary stenosis

Glycans as Key Checkpoints of T Cell Activity and Function

The immune system is highly controlled and fine-tuned by glycosylation, through the addition of a diversity of carbohydrates structures (glycans) to virtually all immune cell receptors. Despite a relative backlog in understanding the importance of glycans in the immune system, due to its inherent complexity, remarkable findings have been highlighting the essential contributions of glycosylation in the regulation of both innate and adaptive immune responses with important implications in the pathogenesis of major diseases such as autoimmunity and cancer. Glycans are implicated in fundamental cellular and molecular processes that regulate both stimulatory and inhibitory immune pathways. Besides being actively involved in pathogen recognition through interaction with glycan-binding proteins (such as C-type lectins), glycans have been also shown to regulate key pathophysiological steps within T cell biology such as T cell development and thymocyte selection; T cell activity and signaling as well as T cell differentiation and proliferation. These effects of glycans in T cells functions highlight their importance as determinants of either self-tolerance or T cell hyper-responsiveness which ultimately might be implicated in the creation of tolerogenic pathways in cancer or loss of immunological tolerance in autoimmunity. This review discusses how specific glycans (with a focus on N-linked glycans) act as regulators of T cell biology and their implications in disease

Loss and Recovery of Mgat3 and GnT-III Mediated E-cadherin N-glycosylation Is a Mechanism Involved in Epithelial-Mesenchymal-Epithelial Transitions

BACKGROUND: N-acetylglucosaminyltransferase-III (GnT-III) is a glycosyltransferase encoded by Mgat3 that catalyzes the addition of β1,4-bisecting-N-acetylglucosamine on N-glycans. GnT-III has been pointed as a metastases suppressor having varying effects on cell adhesion and migration. We have previously described the existence of a functional feedback loop between E-cadherin expression and GnT-III-mediated glycosylation. The effects of GnT-III-mediated glycosylation on E-cadherin expression and cellular phenotype lead us to evaluate Mgat3 and GnT-III-glycosylation role during Epithelial-Mesenchymal-Transition (EMT) and the reverted process, Mesenchymal-Epithelial-Transition (MET). METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the expression profile and genetic mechanism controlling Mgat3 expression as well as GnT-III-mediated glycosylation, in general and specifically on E-cadherin, during EMT/MET. We found that during EMT, Mgat3 expression was dramatically decreased and later recovered when cells returned to an epithelial-like phenotype. We further identified that Mgat3 promoter methylation/demethylation is involved in this expression regulation. The impact of Mgat3 expression variation, along EMT/MET, leads to a variation in the expression levels of the enzymatic product of GnT-III (bisecting GlcNAc structures), and more importantly, to the specific modification of E-cadherin glycosylation with bisecting GlcNAc structures. CONCLUSIONS/SIGNIFICANCE: Altogether, this work identifies for the first time Mgat3 glycogene expression and GnT-III-mediated glycosylation, specifically on E-cadherin, as a novel and major component of the EMT/MET mechanism signature, supporting its role during EMT/MET

Molecular Plasticity of E-Cadherin and Sialyl Lewis X Expression, in Two Comparative Models of Mammary Tumorigenesis

The process of metastasis involves a series of steps and interactions between the tumor embolus and the microenvironment. Key alterations in adhesion molecules are known to dictate progression from the invasive to malignant phenotype followed by colonization at a distant site. The invasive phenotype results from the loss of expression of the E-cadherin adhesion molecule, whereas the malignant phenotype is associated with an increased expression of the carbohydrate ligand-binding epitopes, (e.g. Sialyl Lewis (x/a)) that bind endothelial E-selectin of the lymphatics and vasculature.Our study analyzed the expression of two adhesion molecules, E-cadherin and Sialyl Lewis x (sLe(x)), in both a canine mammary carcinoma and human inflammatory breast cancer (IBC) model, using double labelled immunofluorescence staining.Our results demonstrate that canine mammary carcinoma and human IBC exhibit an inversely correlated cellular expression of E-cadherin and sLe(x) within the same tumor embolus.Our results in these two comparative models (canine and human) suggest the existence of a biologically coordinated mechanism of E-cadherin and sLe(x) expression (i.e. molecular plasticity) essential for tumor establishment and metastatic progression

A memória adaptativa: vantagem do processamento de sobrevivência no defeito cognitivo ligeiro (DCL amnésico)

info:eu-repo/semantics/publishedVersio

E-cadherin immunoprecipitation of CMT-U27 cell line.

<p>The left lane shows the E-cadherin immunoprecipitate. The right lane shows the absence of sLe^x in the E-cadherin immunoprecipitate. The 50 kDa bands in both lanes are the immunoglobulin heavy chain.</p