Single-cell profiling of circulating tumour cells: a great leap forward
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OPINION PAPER
Single-cell profiling of circulating tumour cells: a great leap forward Julien de Naurois
Received: 5 November 2012 / Accepted: 7 November 2012 / Published online: 15 November 2012 # Springer-Verlag Berlin Heidelberg 2012
Much hope lies in the study of circulating tumour cells (CTCs) to provide further breakthroughs in cancer biology as well as better treatments for cancer patients. CTCs are rare, freely circulating epithelial cells originating from primary or secondary tumours. Only within the last 15 years has the technology been available to isolate them from whole blood in patients affected by cancer [7]. CTCs are thought to be an integral part of the metastatic process ultimately responsible for cancer death. Crucially, CTC enumeration is an independent adverse prognostic marker in several advanced cancers including breast [2], colon, lung and prostate [5]. However, it is not yet established which molecular signatures confer CTCs with an ability to form ‘successful’ metastases and which molecular signatures might predict clinical outcomes such as relapse/recurrence or response to certain systemic therapies. The low morbidity associated with collecting CTCs from patients makes them obvious research material, with the hope of developing predictive biomarkers. In parallel with CTC research, the recent demonstration of gene expression heterogeneity within solid tumours by deep exome sequencing [3] has questioned existing practices that rely on molecular phenotypes obtained from single biopsies as foundation for developing biomarkers. Scientists and clinicians working with CTCs are understandably interested in uncovering whether molecular heterogeneity might also be found in CTCs. The paper of Powell et al [6] entitled ‘Single cell profiling of circulating tumour cells: transcriptional heterogeneity and diversity from breast cancer cell lines’ published in PLOS ONE in May 2012 provides answers to this question as well as opening new directions in this research field.
J. de Naurois (*) Cell Biophysics Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK e-mail: [email protected]
Using their own custom-made immunomagnetic separation technology called the MagSweeper, these authors were able to successfully separate live CTCs with high purity from whole blood samples from 50 patients with breast cancer (20 with primary and 30 with metastatic disease). Within this patient cohort, 105 individual CTCs (up to five CTCs per patient) were subjected to an 87-gene expression profile assay, covering genes considered to play important roles in a variety of metabolic processes including metastasis, epithelial-to-mesenchymal (EMT) transition, cell proliferation and stem cell phenotype. In control experiments using single cells from seven breast cancer cell lines, the authors convincingly demonstrated that the MagSweeper did not affect gene expressing itself nor cell viability. From these same cell lines, through hierarchical clustering, it was found t
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