Differential Cadherin Expression: Potential Markers for Epithelial to Mesenchymal Transformation During Tumor Progression

Agiostratidou, Georgia; Hulit, James; Phillips, Greg R.; Hazan, Rachel B.

doi:10.1007/s10911-007-9044-6

Cited by 76 publications

(62 citation statements)

References 56 publications

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“…Neural cadherin is categorized as an invasive cadherin and its expression is associated with increased cell motility and promotion of tumor invasion, and it is frequently up-regulated in cancers in tandem with loss of plasma membrane located E-cadherin. 25 Heterogeneous expression of neural cadherin was observed in CTC and CTM within and between patients, again consistent with a partial EMT phenotype. Figure 3B shows examples of positive neural cadherin staining in CTM (left panel), negative staining of a CTM (middle panel), and examples of a positively and a negatively stained CTC (upper and lower right panel).…”

Section: Mesenchymal Markers Are Heterogeneously Expressed In Ctm Andmentioning

confidence: 80%

Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer

Hou

Krebs

Ward

et al. 2011

The American Journal of Pathology

393

369

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Circulating tumor cell (CTC) number in metastatic cancer patients yields prognostic information consistent with enhanced cell migration and invasion via loss of adhesion, a feature of epithelial-to-mesenchymal transition (EMT). Tumor cells also invade via collective migration with maintained cell-cell contacts and consistent with this is the circulating tumor microemboli (CTM; contiguous groups of tumor cells) that are observed in metastatic cancer patients. Using a blood filtration approach, we examined markers of EMT (cytokeratins, E-cadherin, vimentin, neural cadherin) and prevalence of apoptosis in CTCs and CTM to explore likely mechanism(s) of invasion in lung cancer patients and address the hypothesis that cells within CTM have a survival advantage. Intra-patient and inter-patient heterogeneity was observed for EMT markers in CTCs and CTM. Vimentin was only expressed in some CTCs, but in the majority of cells within CTM; E-cadherin expression was lost, cytoplasmic or nuclear, and rarely expressed at the surface of the cells within CTM. A subpopulation of CTCs was apoptotic, but apoptosis was absent within CTM. This pilot study suggests that EMT is not prosecuted homo- Metastasis usually portends a dismal prognosis for cancer patients and effective therapeutic intervention in the metastatic process remains elusive. This is the case despite decades of research after Paget's "seed and soil" hypothesis in 1889 to explain why primary tumors within one particular organ give rise to secondary tumors at nonrandom sites 1 and Ewing's suggestion in 1929 that mechanical factors associated with the anatomy of human vasculature also determine the final destination of metastasizing tumor cells. 2 It is now apparent that tumor cell invasion and formation of distant metastasis can progress via three major routes: i) via the bloodstream, ii) via lymphatic vessels, and iii) via transcoelomic spread into the pleural, pericardial, and abdominal cavities. 3 The hematogenous system is thought to be the primary and most common route for the formation of distant metastases. Disseminating tumor cells can also circulate to and lie dormant in the bone marrow, potentially for a number of years, and then re-enter the bloodstream en route to secondary metastatic sites. 4 According to the widely espoused epithelial-to-mesenchymal transition (EMT) paradigm, suggested by some as essential for metastasis, 5,6 invading mesenchymal tumor cells lose cell-cell adhesion. Consistent with this concept, there are increasing reports enumerating individual circulating tumor cells (CTCs) in cancer patients' blood samples. Moreover, using the Food and Drug Administration's approved CellSearch platform, the CTC number is a prognostic biomarker in metastatic breast,

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Section: Mesenchymal Markers Are Heterogeneously Expressed In Ctm Andmentioning

confidence: 80%

Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer

Hou

Krebs

Ward

et al. 2011

The American Journal of Pathology

393

369

View full text Add to dashboard Cite

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“…An EMT results from several molecular changes, consisting of a global loss of epithelial markers, including E-cadherin, and an accompanying gain of mesenchymal markers such as N-cadherin (Kuphal and Bosserhoff, 2006;Maeda et al, 2005;Nakajima et al, 2004). In this situation, Ncadherin has a promigratory effect, helping the tumour cells to detach from their normal location and to spread in their environment (Agiostratidou et al, 2007;Hazan et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

N-cadherin expression level modulates integrin-mediated polarity and strongly impacts on the speed and directionality of glial cell migration

Camand

Péglion

Osmani

et al. 2012

Journal of Cell Science

123

107

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SummaryPerturbation of cell polarity is a hallmark of cancer cells. In carcinomas, loss of epithelial E-cadherin contributes to the loss of cell polarity and promotes epithelial-mesenchymal transition and carcinoma infiltration. However, the contribution of classical cadherins to the development of non-epithelial tumours is less well documented. We investigated the impact of the level of N-cadherin expression on the polarity and migration of normal and tumour glial cells. Low levels of N-cadherin were frequently observed in human glioma samples and purified glioma cells. Using a wound-healing assay, we show that a decreased level of N-cadherin promotes a faster and less-directed migration both in normal and tumour cells. N-cadherin-mediated contacts control cell velocity and polarity through the regulation of focal adhesions. In cells expressing low levels of N-cadherin, small focal adhesions are present at the entire cell periphery of confluent cells and are not affected by wounding of the cell monolayer. Under these conditions, wound-induced integrin-mediated recruitment of the small GTPase Cdc42, activation of the Cdc42-mediated polarity pathway and centrosome reorientation do not occur. Re-expression of N-cadherin in gliomas restores cell polarity and strongly reduces cell velocity, suggesting that loss of N-cadherin could contribute to the invasive capacity of tumour astrocytes.

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“…Other studies show that the TNFα, the major inducer of NF-kβ, involves an increase in the formation of MCF-7-MS cells through up-regulation of the Slug gene, a regulator of stem mammary tumour phenotype [30] . TNFα induces, after 10 d of treatment, the acquisition of typical characteristics of BCSCs (CD44 + / CD24 -) in not transformed mammary epithelial cell line MCF-10A; this effect is accompanied by the reduction of the E-cadherin expression and an increase of mesenchymal markers expression such as vimentin and smooth-muscle actin-α (αSMA) [31,32] . These considerations lead to the hypothesis that the survival of the BCSCs is dependent on the activation of NF-kβ, in turn resulting from the stimulation exerted, for example, by pro-inflammatory cytokines, as confirmed by the effect of inhibition of the proliferation of MCF7-MS due to the use of selective inhibitors of the NF-kβ, as parthenolide [33] .…”

Section: Inflammation and Breast Cancer Stromamentioning

confidence: 99%

Role of nuclear receptors in breast cancer stem cells

Papi

Orlandi

2016

WJSC

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The recapitulation of primary tumour heterogenity and the existence of a minor sub-population of cancer cells, capable of initiating tumour growth in xenografts on serial passages, led to the hypothesis that cancer stem cells (CSCs) exist. CSCs are present in many tumours, among which is breast cancer. Breast CSCs (BCSCs) are likely to sustain the growth of the primary tumour mass, as well as to be responsible for disease relapse and metastatic spreading. Consequently, BCSCs represent the most significant target for new drugs in breast cancer therapy. Both the hypoxic condition in BCSCs biology and proinflammatory cytokine network has gained increasing importance in the recent past. Breast stromal cells are crucial components of the tumours milieu and are a major source of inflammatory mediators. Recently, the antiinflammatory role of some nuclear receptors ligands has emerged in several diseases, including breast cancer. Therefore, the use of nuclear receptors ligands may be a valid strategy to inhibit BCSCs viability and consequently breast cancer growth and disease relapse.

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Differential Cadherin Expression: Potential Markers for Epithelial to Mesenchymal Transformation During Tumor Progression

Cited by 76 publications

References 56 publications

Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer

Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer

N-cadherin expression level modulates integrin-mediated polarity and strongly impacts on the speed and directionality of glial cell migration

Role of nuclear receptors in breast cancer stem cells

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