EMT-independent detection of circulating tumor cells in human blood samples and pre-clinical mouse models of metastasis

Kitz, Jenna; Goodale, David; Postenka, Carl O.; Lowes, Lori E.; Allan, Alison L.

doi:10.1007/s10585-020-10070-y

Cited by 19 publications

(15 citation statements)

References 32 publications

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“…Parsortix® separation was demonstrated to identify significantly more mesenchymal human CTCs compared to the clinical CellSearch system. 22 Contrary, MACS® separation is limited by the capture of CTCs of epithelial phenotype, as was already confirmed in our previous study in spiking experiments of human fibroblasts into the buffy coat, demonstrating 0% recovery rate for mesenchymal cell line. 8 CTCs found in the blood of cancer patients are a heterogeneous population as epithelial, mesenchymal and hybrid E/M phenotypes were detected in different cancer types.…”

Section: Discussionsupporting

confidence: 58%

Morphological features of breast cancer circulating tumor cells in blood after physical and biological type of isolation

Jesenko

Modic

Kuhar

et al. 2021

Radiology and Oncology

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Background Circulating tumor cells (CTCs) have become an important biomarker in breast cancer. Different isolation tech-niques based on their biological or physical features were established. Currently, the most widely used methods for visualization after their separation are based on immunofluorescent staining, which does not provide the information on the morphology. Materials and methods The aim of this study was to evaluate how two different separation techniques affect cell morphology and to analyse cell morphology with techniques used in routine cytopathological laboratory. A direct side-by-side comparison of physical (Parsortix®) and biological (MACS®) separation technique was performed. Results In the preclinical setting, both isolation techniques retained the viability and antigenic characteristics of MCF7 breast cancer cells. Some signs of degeneration such as cell swelling, cytoplasmic blebs, villous projections and vacuolization were observed. In metastatic breast cancer patient cohort, morphological features of isolated CTCs were dependent on the separation technique. After physical separation, CTCs with preserved cell morphology were detected. After biological separation the majority of the isolated CTCs were so degenerated that their identity was difficult to confirm. Conclusions Taken together, physical separation is a suitable technique for detection of CTCs with preserved cell morphology for the use in a routine cytopathological laboratory.

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Section: Discussionsupporting

confidence: 58%

Morphological features of breast cancer circulating tumor cells in blood after physical and biological type of isolation

Jesenko

Modic

Kuhar

et al. 2021

Radiology and Oncology

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“…2 , e.g., Parsortix™, CelSee PREP 400™, FCMC, FMSA, MCA, spiral microfluidic devices). Though VyCAP showed decreased recovery rate of epithelial cells in comparison to CellSearch ® , recent report performed on mouse blood with spiked human epithelial BC cancer cell line showed that VyCAP outperforms CellSearch ® in epithelial BC cells recovery [ 180 ]. RRs of cell lines with epithelial and mesenchymal phenotypes were not available for all of the methods, in such cases only one of the phenotypes is shown on Fig.…”

Section: Methods For Mesenchymal Ctcs Isolationmentioning

confidence: 99%

Breast cancer circulating tumor cells with mesenchymal features—an unreachable target?

Topa

Grešner

Żaczek

et al. 2022

Cell. Mol. Life Sci.

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Circulating tumor cells (CTCs) mediate dissemination of solid tumors and can be an early sign of disease progression. Moreover, they show a great potential in terms of non-invasive, longitudinal monitoring of cancer patients. CTCs have been extensively studied in breast cancer (BC) and were shown to present a significant phenotypic plasticity connected with initiation of epithelial-mesenchymal transition (EMT). Apart from conferring malignant properties, EMT affects CTCs recovery rate, making a significant portion of CTCs from patients’ samples undetected. Wider application of methods and markers designed to isolate and identify mesenchymal CTCs is required to expand our knowledge about the clinical impact of mesenchymal CTCs. Therefore, here we provide a comprehensive review of clinical significance of mesenchymal CTCs in BC together with statistical analysis of previously published data, in which we assessed the suitability of a number of methods/markers used for isolation of CTCs with different EMT phenotypes, both in in vitro spike-in tests with BC cell lines, as well as clinical samples. Results of spiked-in cell lines indicate that, in general, methods not based on epithelial enrichment only, capture mesenchymal CTCs much more efficiently that CellSearch® (golden standard in CTCs detection), but at the same time are not much inferior to Cell Search®, though large variation in recovery rates of added cells among the methods is observed. In clinical samples, where additional CTCs detection markers are needed, positive epithelial-based CTCs enrichment was the most efficient in isolating CTCs with mesenchymal features from non-metastatic BC patients. From the marker side, PI3K and VIM were contributing the most to detection of CTCs with mesenchymal features (in comparison to SNAIL) in non-metastatic and metastatic BC patients, respectively. However, additional data are needed for more robust identification of markers for efficient detection of CTCs with mesenchymal features.

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“…Therefore, alternative methods that do not require the EpCAM expression may be necessary to isolate some CTCs and CTC clusters. 77 …”

Section: Isolation Of Ctc Clusters With Microfluidic Systemsmentioning

confidence: 99%

Microfluidic techniques for isolation, formation, and characterization of circulating tumor cells and clusters

et al. 2022

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Circulating tumor cell (CTC) clusters that are shed from the primary tumor into the bloodstream are associated with a poor prognosis, elevated metastatic potential, higher proliferation rate, and distinct molecular features compared to single CTCs. Studying CTC clusters may give us information on the differences in the genetic profiles, somatic mutations, and epigenetic changes in circulating cells compared to the primary tumor and metastatic sites. Microfluidic systems offer the means of studying CTC clusters through the ability to efficiently isolate these rare cells from the whole blood of patients in a liquid biopsy. Microfluidics can also be used to develop in vitro models of CTC clusters and make possible their characterization and analysis. Ultimately, microfluidic systems can offer the means to gather insight on the complexities of the metastatic process, the biology of cancer, and the potential for developing novel or personalized therapies. In this review, we aim to discuss the advantages and challenges of the existing microfluidic systems for working with CTC clusters. We hope that an improved understanding of the role microfluidics can play in isolation, formation, and characterization of CTC clusters, which can lead to increased sophistication of microfluidic platforms in cancer research.

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EMT-independent detection of circulating tumor cells in human blood samples and pre-clinical mouse models of metastasis

Cited by 19 publications

References 32 publications

Morphological features of breast cancer circulating tumor cells in blood after physical and biological type of isolation

Morphological features of breast cancer circulating tumor cells in blood after physical and biological type of isolation

Breast cancer circulating tumor cells with mesenchymal features—an unreachable target?

Microfluidic techniques for isolation, formation, and characterization of circulating tumor cells and clusters

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