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

The cadherin–catenin complex in nasopharyngeal carcinoma

Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and β-catenin function have been implicated in many cancers, but have not been fully explored in nasopharyngeal carcinoma. The aim of this study was to analyze β-Catenin cellular location and E-cadherin expression levels in nasopharyngeal carcinoma. E-cadherin expression levels were also correlated with clinical data and underlying pathology. β-Catenin and E-cadherin expression were examined in 18 nasopharyngeal carcinoma and 7 non-tumoral inflammatory pharynx tissues using immunohistochemical methods. Patient clinical data were collected, and histological evaluation was performed by hematoxylin/eosin staining. β-catenin was detected in membrane and cytoplasm in all cases of nasopharyngeal carcinoma, regardless of histological type; in non-tumoral tissues, however, β-catenin was observed only in the membrane. As for E-cadherin expression levels, strong staining was observed in most non-tumoral tissues, but staining was only moderate in nasopharyngeal carcinoma tissues. E-cadherin expression was associated with β-catenin localization, study group, metastatic disease, and patient outcomes. Reduced levels of E-cadherin protein observed in nasopharyngeal carinoma may play an important role in invasion and metastasis. Cytoplasmic β-catenin in nasopharyngeal carcinoma may impair cell–cell adhesion, promoting invasive behavior and a metastatic tumor phenotype

The cadherin–catenin complex in laryngeal squamous cell carcinoma

Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and β-catenin function have been implicated in many cancers, but have not been fully explored in laryngeal squamous cell carcinoma. In this study, β-catenin cellular location and E-cadherin expression levels were analyzed in 16 laryngeal squamous cell carcinomas (LSCCs) (9 glottic and 7 supraglottic) and 11 samples of non-tumoral inflammatory larynx tissue, using immunohistochemical methods. All non-tumoral tissues showed equally strong membranous expression of β-catenin, while cytoplasmic expression was found in only 3 of the 11 samples. By contrast, whereas 8/9 glottic LSCCs exhibited only membranous expression of β-catenin, 6/7 supraglottic LSCCs displayed both membranous and cytoplasmic expression (p = 0.003). Strong E-cadherin staining was observed in 9/11 non-tumoral tissues and 7/9 glottic LSCCs, whereas 4/7 supraglottic LSCCs exhibited weak expression. Reduced membrane expression of E-cadherin and cytoplasmic retention of β-catenin in supraglottic LSCC seems to be related with more aggressive biological behavior which has been described in clinical studies. Further research is required to clarify the involvement of β-catenin in the mechanism associated with malignant transformation in laryngeal tissues

Selective disruption of the E-cadherin-catenin system by an algal toxin

Yessotoxins (YTXs) are algal toxins that can be accumulated in edible molluscs. YTX treatment of MCF-7 breast cancer cells causes the accumulation of a 100 kDa fragment of E-cadherin, which we have named ECRA(100). A relative decrease in the concentrations of intact E-cadherin did not accompany the accumulation of ECRA(100) in cytosoluble extracts of MCF-7 cells on the first day of YTX treatment, but a collapse of the E-cadherin system was detected after 2-5 days of treatment with the toxin. An analysis of the general structure of ECRA(100) revealed that it consists of an E-cadherin fragment lacking the intracellular domain of the protein. ECRA(100) was not released into culture media of YTX-treated cells. Accumulation of ECRA(100) was observed in other epithelial cells, such as human intestine Caco-2 and MDCK cells after treatment with YTX. In turn, YTX could not induce accumulation of fragments of other members of the cadherin family, such as N-cadherin in the PC 12 cell line and K-cadherin in sensitive cells (MCF-7, Caco-2, MDCK). The accumulation of a 100 kDa fragment of E-cadherin devoid of its intracellular domain induced by YTX was accompanied by reduced levels of beta- and gamma-catenins bound to E-cadherin, without a concomitant decrease in the total cytosoluble pools of beta- and gamma-catenins. Taken together, the results we obtained show that YTX causes the selective disruption of the E-cadherin-catenin system in epithelial cells, and raise some concern about the potential that an algal toxin found in seafood might disrupt the tumour suppressive functions of E-cadherin