Multiple isolation techniques have been developed in recent years, the CellSearch ®system being the only one cleared by the FDA for clinical use in patients with breast, colon and prostate cancer.
Moreover, to reach the blood circulation,CTCs undergoan epithelial-to-mesenchymal transition process (EMT) and mesenchymal-to-epithelial transition (MET), giving rise to thewide variety of CTC phenotypes that have been described in the bloodstream. They can escape anoikis, travelling with blood cellsand forming aggregates. ĬTCs have developed several mechanisms to survive in the blood andreach distant organs.
Although many advances have been made regarding the detection and molecular characterisation of CTCs, several challenges still exist precluding the clinical use of CTCs in early detection and their characterisation as an important tool to monitor and prevent the development of overt metastatic disease. The isolation of CTCs presents a significant challenge because: i) CTCs are rare events in blood (the estimation is just 1 CTC per ~10 7 white blood cells per millilitre of blood) ii) the blood volume available for CTCs detection in the clinical routine is limited (7.5 mL blood) iii) there are no CTC-specific or universal markers. Metastasis remains the main cause of cancer-related deaths, dissemination through the blood circulation being the frontier between favourable localised and unfavourable systemic disease.Circulating tumour cells (CTCs) are tumour cells shed from an existing primary tumour or from metastatic lesions that circulate in the peripheral blood of patients with solid malignancies. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: This work was supported by Axencia Galega de Innovación (Xunta de Galicia) and InveNNta (Innovation in Nanomedicine), co-financed by the European Union (EU) through the Operational Programme for Cross-border Cooperation: Spain-Portugal (POCTEP 2007-2013), and European Regional Development Fund (ERDF).Ĭompeting interests: The authors have declared that no competing interests exist. Received: JanuAccepted: SeptemPublished: October 6, 2016Ĭopyright: © 2016 Vila et al. PLoS ONE 11(10):Įditor: Jung Weon Lee, Seoul National University College of Pharmacy, REPUBLIC OF KOREA (2016) EGFR-Based Immunoisolation as a Recovery Target for Low-EpCAM CTC Subpopulation. Besides EpCAM, we propose Epidermal Growth Factor Receptor (EGFR) as an additional isolation marker for efficient CTCs detection.Ĭitation: Vila A, Abal M, Muinelo-Romay L, Rodriguez-Abreu C, Rivas J, López-López R, et al. We next developed customised polystyrene magnetic beads coated with antibodies to efficiently isolate the phenotypically different subpopulations of CTCs from the peripheral blood mononuclear cells (PBMCs) of patients with metastatic cancer. In this work, we first characterised a panel of cell lines representative of tumour heterogeneity, confirming the existence of tumour cell subpopulations with restricted epithelial features and supporting the limitations of EpCAM-based technologies. The controversy stems from the impact that the more aggressive mesenchymal tumour phenotypes might have on the whole CTC population. CTCs are rare events in the blood of patients and are believed to represent the epithelial population from a primary tumour of epithelial origin, thus EpCAM immunoisolation is considered an appropriate strategy. Moreover, efforts to develop new strategies for CTCs isolation and characterisation, and the translation of CTCs into clinical practice needs to overcome the limitation associated with the sole use of Epithelial Cell Adhesion Molecule (EpCAM) expression to purify this tumour cell subpopulation. Circulating tumour cells (CTCs) play a key role in the metastasis process, as they are responsible for micrometastasis and are a valuable tool for monitoring patients in real-time.