EpCAM-independent capture of circulating tumor cells with a ‘universal CTC-chip’

Chikaishi, Yasuhiro; Yoneda, Kazue; Ohnaga, Takashi; Tanaka, Fumihiro

doi:10.3892/or.2016.5235

Cited by 52 publications

(65 citation statements)

References 15 publications

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“…The CTC-test provided a significant prognostic value in discrimination between MM patients and non-MM patients such as asbestos pleurisy (P=0.036), but the sensitivity was only modest (32.7%) mainly due to negative or low expression of EpCAM on MM cells, which may not be effectively captured with an anti-EpCAM antibody (13). These results clearly indicate the need for a sensitive system for capture EpCAM-negative CTCs, and we have developed a high efficient system to capture CTCs using a microfluidic device 'CTC-chip' (14,15). In the system, CTCs are captured to numerous micro-posts coated with an antibody against an antigen expressed on target tumor cells, and the most important advantage is capability of conjugating any antibody to capture CTCs.…”

Section: Introductionmentioning

confidence: 98%

“…The cell capture efficiency was represented as N-captured/N-total (14,15). The average and standard error (SE) of capture efficiency were calculated from results obtained in triplicated experiments.…”

Section: Preparation Of Ctc-chipmentioning

confidence: 99%

“…Sample preparation and flow test were performed as described previously (15). In brief, 500 tumor cells, labeled with CellTrace™ CFSE Cell Proliferation Kit (Thermo Fisher Scientific, Inc.) and suspended in 1 ml of phosphate-buffered saline (PBS) containing 5% BSA were applied to the CTC-chip system.…”

Section: Preparation Of Ctc-chipmentioning

confidence: 99%

“…The polymeric CTC-chip system was used after two-step coating with an antibody to capture CTCs as described previously (15). In brief, the chip was first incubated with a goat anti-mouse IgG antibody (SouthernBiotech, Birmingham, AL, USA), and then was incubated with an anti-EpCAM antibody (clone HEA125), an anti-podoplanin antibody, or an anti-mesothelin antibody (clone K1) to capture tumor cells; the antibody-coated chip was referred to as 'EpCAM-chip', 'podoplanin-chip', and 'mesothelin-chip', respectively.…”

Section: Preparation Of Ctc-chipmentioning

confidence: 99%

“…In the system, CTCs are captured to numerous micro-posts coated with an antibody against an antigen expressed on target tumor cells, and the most important advantage is capability of conjugating any antibody to capture CTCs. In fact, we effectively captured and isolated EpCAM-negative MM cells (ACC-MESO-4 cells) with the CTC-chip coated with an antibody against a mesothelial marker (podoplanin) (15), indicating its potential capability of capturing a wide variety of CTCs by conjugating appropriate capture antibodies. In the current study, we expand and examined capture efficiencies of the 'universal' CTC-chip for another MM cell-line (ACC-MESO-1) and with another capture antibody against another mesothelial marker (mesothelin) to improve sensitivity in detection of CTCs for clinical application in the diagnosis of MM.…”

Section: Introductionmentioning

confidence: 99%

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Capture of mesothelioma cells with ‘universal’ CTC-chip

et al. 2017

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Abstract. Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system. Accordingly, the authors developed a novel microfluidic system to capture CTCs (CTC-chip), and demonstrated that the CTC-chip effectively captured MM cells (ACC-MESO-4) spiked in the blood by conjugating an anti-podoplanin antibody. The results of the present study demonstrated that the CTC-chip coated with the anti-podoplanin antibody captured another MM cell (ACC-MESO-1). However, the capture efficiencies were lower than those for ACC-MESO-4. In addition, an anti-mesothelin antibody was used to capture CTCs, however the CTC-chip coated with the anti-mesothelin antibody failed to effectively capture MM cells, possibly due to low mesothelin expression. Overall, the CTC-chip may capture specific types of CTCs by conjugating any antibody against an antigen expressed on CTCs, and may be a useful system for the diagnosis of malignant tumors, including MM.

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Section: Introductionmentioning

confidence: 98%

Section: Preparation Of Ctc-chipmentioning

confidence: 99%

Section: Preparation Of Ctc-chipmentioning

confidence: 99%

Section: Preparation Of Ctc-chipmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Capture of mesothelioma cells with ‘universal’ CTC-chip

et al. 2017

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Magnetically driven microfluidics for isolation of circulating tumor cells

Luo

2020

Cancer Medicine

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Circulating tumor cells (CTCs) largely contribute to cancer metastasis and show potential prognostic significance in cancer isolation and detection. Miniaturization has progressed significantly in the last decade which in turn enabled the development of several microfluidic systems. The microfluidic systems offer a controlled microenvironment for studies of fundamental cell biology, resulting in the rapid development of microfluidic isolation of CTCs. Due to the inherent ability of magnets to provide forces at a distance, the technology of CTCs isolation based on the magnetophoresis mechanism has become a routine methodology. This historical review aims to introduce two principles of magnetic isolation and recent techniques, facilitating research in this field and providing alternatives for researchers in their study of magnetic isolation. Researchers intend to promote effective CTC isolation and analysis as well as active development of next‐generation cancer treatment. The first part of this review summarizes the primary principles based on positive and negative magnetophoretic isolation and describes the metrics for isolation performance. The second part presents a detailed overview of the factors that affect the performance of CTC magnetic isolation, including the magnetic field sources, functionalized magnetic nanoparticles, magnetic fluids, and magnetically driven microfluidic systems.

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An Integrated Microfluidic Chip and Its Clinical Application for Circulating Tumor Cell Isolation and Single‐Cell Analysis

Zhao

Chen

et al. 2019

Cytometry Pt A

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Circulating tumor cells (CTCs) represent invasive tumor cell populations and provide a noninvasive solution to the clinical management and research of tumors. Characterization of CTCs at single‐cell resolution enables the comprehensive understanding of tumor heterogeneity and may benefit the diagnosis and treatment of cancer patients. However, most efforts have been made on enumeration and detection of CTCs, while little focus has been directed to single‐cell study. Herein, an integrated microfluidic platform for single‐cell isolation and analysis was established. After validating this platform on lung cancer cell lines, we detected and isolated single CTCs from the peripheral blood samples of 20 cancer patients before and after one treatment cycle. Furthermore, we performed single‐cell whole‐exome DNA sequencing on a single CTC from the peripheral blood sample of a representative early stage lung cancer patient. Among the blood samples of 20 patients, 15 of them were positive for CTC detection (75.0% detectable rate). Single‐cell analysis revealed detailed genetic variations of the CTC, while six new gene mutations were detected in both single CTC and surgical specimen. This study provides a useful tool for the isolation and analysis of single CTCs from peripheral blood samples, which not only facilitates the early diagnosis of cancers but also helps to unravel the genetic information of tumor at a single‐cell level. © 2019 International Society for Advancement of Cytometry

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EpCAM-independent capture of circulating tumor cells with a ‘universal CTC-chip’

Cited by 52 publications

References 15 publications

Capture of mesothelioma cells with ‘universal’ CTC-chip

Capture of mesothelioma cells with ‘universal’ CTC-chip

Magnetically driven microfluidics for isolation of circulating tumor cells

An Integrated Microfluidic Chip and Its Clinical Application for Circulating Tumor Cell Isolation and Single‐Cell Analysis

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