Abstract

BackgroundSialyl Lewis x (sLex) 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 sLex is 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.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.The aim of this study was to analyse the sLex expression in canine malignant mammary tumours and to evaluate if the presence of sLex correlates with the expression of E-Cadherin and with clinicopathological features.MethodsFifty-three cases of canine mammary carcinomas were analysed immunohistochemically using monoclonal antibodies against sLex (IgM) and E-Cadherin (IgG). The clinicopathological data were then assessed to determine whether there was a correlation with sLex tumour expression. Double labelled immunofluorescence staining was performed to analyse the combined expression of sLex and E-Cadherin.ResultssLex expression was consistently demonstrated in all cases of canine mammary carcinomas with different levels of expression. We found a significant relationship between the levels of sLex expression and the presence of lymph node metastases. We also demonstrated that when E-Cadherin expression was increased sLex was reduced and vice-versa. The combined analysis of both adhesion molecules revealed an inverse relationship.ConclusionIn the present study we demonstrate the importance of sLex in the malignant phenotype of canine malignant mammary tumours. Our results support the use of sLex as a prognostic tumour marker in canine mammary carcinomas. Furthermore, we showed that sLex and E-Cadherin expression were inversely correlated. Future studies are warranted to clarify the molecular mechanism underlying the relation between sLex and E-Cadherin in canine mammary carcinoma cells which represents an important comparative model to woman breast cancer.

Highlights

  • Sialyl Lewis x antigen is a carbohydrate antigen that is considered a marker for cancer and implicated functionally in the malignant behaviour of cancer cells

  • We found a significant relationship between the levels of Sialyl Lewis x (sLex) expression and the presence of lymph node metastases

  • We demonstrated that when E-Cadherin expression was increased sLex was reduced and vice-versa

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Summary

Introduction

Sialyl Lewis x (sLex) antigen is a carbohydrate antigen that is considered a marker for cancer and implicated functionally in the malignant behaviour of cancer cells. In general canine malignant tumours metastasise via the lymphatics to the regional lymph nodes or hematogenously to the lungs that represent the most common site of distant metastases. It is generally accepted that every step of the metastatic cascade is dependent on specific adhesive interactions of cancer cells with other cells and components of the extracellular matrix. These interactions are mediated by different families of adhesion molecules including cadherins, integrins, members of the immunoglobulin superfamily, and selectins and their carbohydrate ligands – Sialyl Lewis a (sLea) and sLex [9,13,14]

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