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

Salomé S Pinho,Fátima Gärtner,Celso A Reis,Mary L Alpaugh,Immo A Hansen

doi:10.1371/journal.pone.0006636

Salomé S Pinho, Fátima Gärtner + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0006636

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Journal: PLoS ONE	Publication Date: Aug 13, 2009
Citations: 34	License type: CC BY 4.0

Affiliation: University of Porto, City College of New York

Abstract

BackgroundThe 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.MethodologyOur study analyzed the expression of two adhesion molecules, E-cadherin and Sialyl Lewis x (sLex), in both a canine mammary carcinoma and human inflammatory breast cancer (IBC) model, using double labelled immunofluorescence staining.ResultsOur results demonstrate that canine mammary carcinoma and human IBC exhibit an inversely correlated cellular expression of E-cadherin and sLex within the same tumor embolus.ConclusionsOur results in these two comparative models (canine and human) suggest the existence of a biologically coordinated mechanism of E-cadherin and sLex expression (i.e. molecular plasticity) essential for tumor establishment and metastatic progression.

Highlights

Metastasis is classically defined as the lymphatic or haematogenous dissemination of cancer cells from the primary tumor to lymph nodes and/or to distant sites in the body [1]
Our results demonstrate that canine mammary carcinoma and human inflammatory breast cancer (IBC) exhibit an inversely correlated cellular expression of E-cadherin and Sialyl Lewis x (sLex) within the same tumor embolus
In this report we demonstrate that canine mammary carcinoma and the highly metastatic inflammatory breast cancer (IBC) in women, exhibit an inversely correlated expression of E-cadherin and sLex in cells of the same tumor embolus

Summary

Introduction

Metastasis is classically defined as the lymphatic or haematogenous (blood-born) dissemination of cancer cells from the primary tumor (origin) to lymph nodes and/or to distant sites in the body [1]. Even in the most malignant primary tumor not all cells have the capability of successfully colonizing at a distant site [5] This diversity, as well as the molecular and cellular mechanisms underlying the metastatic potential of the tumor embolus result from inherent (clonal selection) or acquired (adaptive) traits or both of the tumor cells composing it [6,7]. A portion of those heterogeneous cells progress to the malignant phenotype and even a smaller portion can successfully colonize, and form deadly metastases [6]. The ability of those tumor cells to conform to new environments is due to a molecular plasticity. The invasive phenotype results from the loss of expression of the Ecadherin 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

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