scholarly journals Cooperative and Escaping Mechanisms between Circulating Tumor Cells and Blood Constituents

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1382 ◽  
Author(s):  
Garrido-Navas ◽  
de Miguel-Perez ◽  
Exposito-Hernandez ◽  
Bayarri ◽  
Amezcua ◽  
...  
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Blood Constituents ◽  
Commensal Microbiota ◽  
Underlying Mechanisms

Metastasis is the leading cause of cancer-related deaths and despite measurable progress in the field, underlying mechanisms are still not fully understood. Circulating tumor cells (CTCs) disseminate within the bloodstream, where most of them die due to the attack of the immune system. On the other hand, recent evidence shows active interactions between CTCs and platelets, myeloid cells, macrophages, neutrophils, and other hematopoietic cells that secrete immunosuppressive cytokines, which aid CTCs to evade the immune system and enable metastasis. Platelets, for instance, regulate inflammation, recruit neutrophils, and cause fibrin clots, which may protect CTCs from the attack of Natural Killer cells or macrophages and facilitate extravasation. Recently, a correlation between the commensal microbiota and the inflammatory/immune tone of the organism has been stablished. Thus, the microbiota may affect the development of cancer-promoting conditions. Furthermore, CTCs may suffer phenotypic changes, as those caused by the epithelial–mesenchymal transition, that also contribute to the immune escape and resistance to immunotherapy. In this review, we discuss the findings regarding the collaborative biological events among CTCs, immune cells, and microbiome associated to immune escape and metastatic progression.

scholarly journals Circulating Tumor Cells: Liquid Biopsy of Cancer

2013 ◽  
Vol 59 (1) ◽  
pp. 110-118 ◽  
Author(s):  
Catherine Alix-Panabières ◽  
Klaus Pantel
Keyword(s):  
Tumor Cells ◽  
Molecular Characterization ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Analytical Sensitivity ◽  
Metastatic Progression ◽  
Level Of Evidence ◽  
Mesenchymal Transition ◽  
Detection Techniques ◽  
Metastatic Relapse

BACKGROUND The detection and molecular characterization of circulating tumor cells (CTCs) are one of the most active areas of translational cancer research, with >400 clinical studies having included CTCs as a biomarker. The aims of research on CTCs include (a) estimation of the risk for metastatic relapse or metastatic progression (prognostic information), (b) stratification and real-time monitoring of therapies, (c) identification of therapeutic targets and resistance mechanisms, and (d) understanding metastasis development in cancer patients. CONTENT This review focuses on the technologies used for the enrichment and detection of CTCs. We outline and discuss the current technologies that are based on exploiting the physical and biological properties of CTCs. A number of innovative technologies to improve methods for CTC detection have recently been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems. Molecular-characterization studies have indicated, however, that CTCs are very heterogeneous, a finding that underscores the need for multiplex approaches to capture all of the relevant CTC subsets. We therefore emphasize the current challenges of increasing the yield and detection of CTCs that have undergone an epithelial–mesenchymal transition. Increasing assay analytical sensitivity may lead, however, to a decrease in analytical specificity (e.g., through the detection of circulating normal epithelial cells). SUMMARY A considerable number of promising CTC-detection techniques have been developed in recent years. The analytical specificity and clinical utility of these methods must be demonstrated in large prospective multicenter studies to reach the high level of evidence required for their introduction into clinical practice.

scholarly journals Development and Validation for Prognostic Nomogram of Epithelial Ovarian Cancer Recurrence based on Circulating Tumor Cells and Epithelial–Mesenchymal Transition

2020 ◽  
Author(s):  
Jiani Yang ◽  
Jun Ma ◽  
Yue Jin ◽  
Shanshan Cheng ◽  
Shan Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Stratification ◽  
Epithelial Ovarian Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Ca 125 ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Significant Difference

Abstract We aimed to determine prognosis value of circulating tumor cells(CTCs) undergoing epithelial–mesenchymal transition(EMT) in epithelial ovarian cancer(EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan–Meier analysis among training group(n=114) and validation group(n=38). By regression screening, both CTC counts(HR 1.187; 95%CI 1.098-1.752; p=0.012) and M-CTC(HR 1.098; 95%CI 1.047-1.320; p=0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites and CA-125 were also collected(p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive value for nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts(p=0.0241), M-CTC(p=0.0107) and the nomogram(p=0.0021) were drawn with significant difference. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration: Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016

scholarly journals Heterogeneity in Circulating Tumor Cells: The Relevance of the Stem-Cell Subset

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 483 ◽  
Author(s):  
Chiara Agnoletto ◽  
Fabio Corrà ◽  
Linda Minotti ◽  
Federica Baldassari ◽  
Francesca Crudele ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Subset ◽  
Intermediate Phenotype ◽  
Current Evidence ◽  
Early Event ◽  
Tumor Type ◽  
Mesenchymal Transition ◽  
Immunodeficient Mice

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process. The analysis of CTCs in patients has recently received widespread attention because of its clinical implications, particularly for precision medicine. Accumulated evidence documents a large heterogeneity in CTCs across patients. Currently, the most accepted view is that tumor cells with an intermediate phenotype between epithelial and mesenchymal have the highest plasticity. Indeed, the existence of a meta-stable or partial epithelial–mesenchymal transition (EMT) cell state, with both epithelial and mesenchymal features, can be easily reconciled with the concept of a highly plastic stem-like state. A close connection between EMT and cancer stem cells (CSC) traits, with enhanced metastatic competence and drug resistance, has also been described. Accordingly, a subset of CTCs consisting of CSC, present a stemness profile, are able to survive chemotherapy, and generate metastases after xenotransplantation in immunodeficient mice. In the present review, we discuss the current evidence connecting CTCs, EMT, and stemness. An improved understanding of the CTC/EMT/CSC connections may uncover novel therapeutic targets, irrespective of the tumor type, since most cancers seem to harbor a pool of CSCs, and disclose important mechanisms underlying tumorigenicity.

scholarly journals Tissue Factor Induced by Epithelial–Mesenchymal Transition Triggers a Procoagulant State That Drives Metastasis of Circulating Tumor Cells

2016 ◽  
Vol 76 (14) ◽  
pp. 4270-4282 ◽  
Author(s):  
Morgane Bourcy ◽  
Meggy Suarez-Carmona ◽  
Justine Lambert ◽  
Marie-Emilie Francart ◽  
Hélène Schroeder ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Circulating Tumor Cells: A Review of Non–EpCAM-Based Approaches for Cell Enrichment and Isolation

2016 ◽  
Vol 62 (4) ◽  
pp. 571-581 ◽  
Author(s):  
Marta Tellez Gabriel ◽  
Lidia Rodriguez Calleja ◽  
Antoine Chalopin ◽  
Benjamin Ory ◽  
Dominique Heymann
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Carcinoma Cells ◽  
Biological Information ◽  
Cell Level ◽  
Benign Diseases ◽  
Mesenchymal Transition ◽  
Advantages And Disadvantages ◽  
Cell Enrichment

Abstract BACKGROUND Circulating tumor cells (CTCs) are biomarkers for noninvasively measuring the evolution of tumor genotypes during treatment and disease progression. Recent technical progress has made it possible to detect and characterize CTCs at the single-cell level in blood. CONTENT Most current methods are based on epithelial cell adhesion molecule (EpCAM) detection, but numerous studies have demonstrated that EpCAM is not a universal marker for CTC detection because it fails to detect both carcinoma cells that undergo epithelial-mesenchymal transition (EMT) and CTCs of mesenchymal origin. Moreover, EpCAM expression has been found in patients with benign diseases. A large proportion of the current studies and reviews about CTCs describe EpCAM-based methods, but there is evidence that not all tumor cells can be detected using this marker. Here we describe the most recent EpCAM-independent methods for enriching, isolating, and characterizing CTCs on the basis of physical and biological characteristics and point out the main advantages and disadvantages of these methods. SUMMARY CTCs offer an opportunity to obtain key biological information required for the development of personalized medicine. However, there is no universal marker of these cells. To strengthen the clinical utility of CTCs, it is important to improve existing technologies and develop new, non–EpCAM-based systems to enrich and isolate CTCs.

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