Detection of EpCAM-Negative and Cytokeratin-Negative Circulating Tumor Cells in Peripheral Blood

Mikolajczyk, Stephen D.; Millar, Lisa S.; Tsinberg, Pavel; Coutts, Stephen M.; Zomorrodi, Maryam; Pham, Tam N.; Bischoff, Farideh Z.; Pircher, Tony J.

doi:10.1155/2011/252361

Cited by 232 publications

(201 citation statements)

References 36 publications

(47 reference statements)

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“…It has also been reported that high EpCAM expression has a negative correlation with the prognosis of patients. The patients who have EpCAM positive cells often have poor prognoses, with concrete manifestations including a high postoperative recurrence rate and a higher lymph node metastasis rate (Mikolajczyk et al, 2011). No such results, however, are available for patients with colon cancers.…”

Section: Discussionmentioning

confidence: 99%

Expression of EpCAM and Wnt/ β-catenin in human colon cancer

Zhou¹,

Qi²,

Xu³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The aims of this study were to explore the correlation between the expression of EpCAM and the Wnt/β-catenin pathway in human colon cancer and its clinical significance for the evaluation of cancer prognosis. Samples from colon cancer, para-carcinoma, or benign intestinal tissue from individual patients (50) and from normal intestinal mucosal tissues (20) were obtained from the Pathology Department of the Shandong Province Binzhou People's Hospital (Shandong, China). Immunohistochemistry was used to detect the expression levels of EpCAM and β-catenin proteins in these tissues, and the prognoses of the patients from whom the samples were derived were determined on follow-up examination. The corresponding in vitro mechanistic siRNA experiments were subsequently performed in the human colon cancer cell line HCT116 to observe the regulatory effects of silencing EpCAM expression on the Wnt/β-catenin pathway. From these analyses, we determined that the expression levels of EpCAM and β-catenin were higher in cancer tissues compared with other tissues 4486©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 4485-4494 (2015) from the same patient, and that the expression of EpCAM and Wnt/β-catenin in colon cancers were positively correlated. The prognostic analysis showed an inverse correlation between EpCAM and Wnt/β-catenin expression and patient prognosis. A further examination of cellular mechanisms confirmed that the silencing of EpCAM led to decreased expression of Wnt/β-catenin, and thus reduced proliferation and increased the apoptosis ratio in the cells. These results suggest that suppression of EpCAM might be a new approach for treating colon cancer.

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Section: Discussionmentioning

confidence: 99%

Expression of EpCAM and Wnt/ β-catenin in human colon cancer

Zhou¹,

Qi²,

Xu³

et al. 2015

Genet. Mol. Res.

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“…Although proved to be diagnostically useful, EpCAM and different types of CKs are, however, discussed to be insufficient to detect the entire population of CTCs in blood [14,25]. The yields of CTCs identified with these sets of markers are frequently poor even in some highly aggressive types of tumors (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…The capture efficiency of these methods heavily depends on EpCAM expression. However, the heterogeneity of EpCAM expression exists in different tumor cells, and it is even absent in some nonepithelial tumors [14]. To overcome the problem, new CTC isolation methods based on cells' physical properties (i.e.…”

Section: Introductionmentioning

confidence: 99%

Introducing, OncoTarget

Blagosklonny¹,

Gudkov²

2010

Oncotarget

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Circulating tumor cells (CTCs) have attracted pretty much attention from scientists because of their important relationship with the process of metastasis. Here, we developed a size-based microfluidic chip containing triangular pillar array and filter channel array for detecting single CTCs and CTC clusters independent of tumor-specific markers. The cell populations in chip were characterized by immune-fluorescent staining combining an epithelial marker and a mesenchymal marker. We largely decreased the whole time of detection process to nearly 1.5h with this microfluidic device. The CTCs were subsequently measured in 77 patients with lung cancer and 39 healthy persons. The microfluidic device allowed for the detection of CTCs with apparent high sensitivity and specificity (82.7% sensitivity and 100% specificity). Furthermore, the total CTC counts were found to be elevated in advanced patients with metastases when compared with those without (20.89±14.57 vs 8.428±5.858 cells/ mL blood; P<0.01). Combined epithelial marker and mesenchymal marker analysis of CTCs could provide more information about metastasis in patients than only usage of epithelial marker. In conclusion, the development of the size-based microfluidic device for efficient capture of CTCs will enable detailed characterization of their biological properties and values in cancer diagnosis.

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“…25 The measurements of the relative mRNAs from 3D on-chip and on-dish cultures (see Supplementary Figure S5) provided further indication that these cells derived from the chip exist in a mesenchymal-like cell state, which more closely resembles those that have undergone EMT than those from 3D on-dish culture. Moreover, Figure 5d presents results of expressions of CD326/EpCAM (broadly expressed on cells of epithelial origin and on epithelium-derived tumor cells 26 ) and vimentin (often used as a marker of mesenchymally derived cells 27 ). For 3D on-chip culture, the reduction in epithelial cell adhesion is evident by a marked decrease in CD326 expression and a gain in vimentin expression, which are two classic features of EMT, compared with that obtained from 2D on-dish culture.…”

Section: Configurable 2d Cell Patterningmentioning

confidence: 99%

Configurable 2D and 3D spheroid tissue cultures on bioengineered surfaces with acquisition of epithelial–mesenchymal transition characteristics

et al. 2012

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Both two-dimensional (2D) and three-dimensional (3D) biomaterial-based culture platforms that are capable of mimicking the in vivo microenvironment to recapitulate the physiological conditions are vital tools in a wide range of cellular and clinical research. Here we report tissue cultures in a microfluidic chip that allows deterministic patterning of cells in 2D/3D. The chip contains a cell-supporting membrane bioengineered to attain either 2D or 3D cell patterns by selectable deposition of extracellular matrix molecules. Results show a cell-trapping rate as high as 97% in our microchip. Tuning of the surface enables not only highly controlled geometry of the monolayer (2D) cell mass but also 3D culture of uniformly sized multicellular spheroids. The 3D spheroid culture of human epithelial ovarian cancer cells in the microfluidic chip resulted in acquisition of mesenchymal traits-increased expressions of N-cadherin, vimentin and fibronectin-and lowered expression of epithelial marker (CD326/epithelial cell adhesion molecule) compared with that in traditional 2D cultures, which is indicative of epithelial-mesenchymal transition in the spheres. In conclusion, these results offer new opportunities to achieve active control of 2D cellular patterns and 3D multicellular spheroids on demand, and may be amenable toward the study of the metastatic processes by in vitro modeling.

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Detection of EpCAM-Negative and Cytokeratin-Negative Circulating Tumor Cells in Peripheral Blood

Cited by 232 publications

References 36 publications

Expression of EpCAM and Wnt/ β-catenin in human colon cancer

Expression of EpCAM and Wnt/ β-catenin in human colon cancer

Introducing, OncoTarget

Configurable 2D and 3D spheroid tissue cultures on bioengineered surfaces with acquisition of epithelial–mesenchymal transition characteristics

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