Circulating tumor microemboli: Progress in molecular understanding and enrichment technologies |
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Authors: | Muhammad Umer Ramanathan Vaidyanathan Nam-Trung Nguyen Muhammad J.A. Shiddiky |
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Affiliation: | 1. Queensland Micro- and Nanotechnology Centre (QMNC), Griffith University, Nathan Campus, QLD 4111, Australia;2. Department of Biomedical Engineering, National University of Singapore (NUS), 117581, Singapore;3. School of Environment and Science, Griffith University, Nathan Campus, QLD 4111, Australia |
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Abstract: | Circulating tumor cells (CTCs) and their clusters, also known as circulating tumor microemboli (CTM), have emerged as valuable tool that can provide mechanistic insights into the tumor heterogeneity, clonal evolution, and stochastic events within the metastatic cascade. However, recent investigations have hinted that CTM may not be mere aggregates of tumor cells but cells comprising CTM exhibit distinct phenotypic and molecular characteristics in comparison to single CTCs. Moreover, in many cases CTM demonstrated higher metastatic potential and resistance to apoptosis as compared to their single cell counterparts. Thus, their evaluation and enumeration may provide a new dimension to our understanding of cancer biology and metastatic cancer spread as well as offer novel theranostic biomarkers. Most of the existing technologies for isolation of hematogenous tumor cells largely favor single CTCs, hence there is a need to devise new approaches, or re-configure the existing ones, for specific and efficient CTM isolation. Here we review existing knowledge and insights on CTM biology. Furthermore, a critical commentary on current and emerging trends in CTM enrichment and characterization along with recently developed ex-vivo CTC expansion methodologies is presented with the aim to facilitate researchers to identify further avenues of research and development. |
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Keywords: | Circulating tumor cells (CTCs) Circulating tumor microemboli (CTM) CTC clusters Metastasis Epithelial to mesenchymal transition (EMT) CTC circulating tumor cells CTM circulating tumor microemboli VEGF-A vascular endothelial growth factor A DCIS ductal carcinoma in situ DTC disseminated tumor cells EMT epithelial-mesenchymal transition ECM extracellular matrix SCLC small cell lung cancer K14 keratin 14 TGF-β transforming growth factor β MET mesenchymal-epithelial transition FGF fibroblast growth factor HER2 human epithelial growth factor receptor 2 EGFR epidermal growth factor receptor PSA prostate specific antigen CK cytokeratin WBC white blood cells ISET isolation by size of epithelial cells CAM collagen adhesion matrix FMS flexible micro spring array iFISH immuno-Fluorescence in situ Hybridization eDAR ensemble-decision aliquot ranking APD avalanche photodiodes HB-Chip herringbone chip DLD deterministic lateral displacement PDMS poly(dimethylsiloxane) SLB supported lipid bilayer CMx cells captured in maximum PMMA poly(methyl methacrylate CRC colorectal cancer MCA microcavity array DFF dean flow fractionation RBC red blood cells |
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