Essentials of circulating tumor cells for clinical research and practice (original) (raw)
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What's new on circulating tumor cells? A meeting report
Breast Cancer Research, 2010
Current research on circulating tumor cells (CTCs) present in the peripheral blood and disseminated tumor cells (DTCs) present in bone marrow provides new insight into the biology of tumor dormancy and tumor cell dissemination and will open new avenues for the early detection of metastatic spread and its successful treatment . Th e 7th International Symposium on Minimal Residual Cancer, organized by Evi Lianidou, Dimitris Mavroudis, and Klaus Pantel, was held in Athens, Greece on 16 to 19 September 2009. Th e symposium brought together 220 basic and clinical researchers who presented cutting-edge research and had an excellent opportunity to have stimulating intense discussions on new technologies and clinical implications of CTC/ DTC detection. We summarize in this report the major fi ndings presented by invited speakers of this meeting. ) presented a vivid account of metastasis sup pres sors, and especially breast cancer metastasis suppres sor 1 (BRMS1), which is signifi cantly downregulated in metastatic disease by epigenetic silencing [2] and co ordinately regulates expression of multiple metastasis-associated micro RNAs [3]. BRMS1 diff erentially attenu ates cellular responses to mitogenic signals at varying steps within the same signaling cascade, and specifi c modu lation of signaling responses received from the micro environment may ultimately dictate which environ ments are permissive or restrictive for tumor cell growth .
Cancers, 2013
Circulating Tumor Cells (CTC) are rare cells originated from tumors that travel into the blood stream, extravasate to different organs of which only a small fraction will develop into metastasis. The presence of CTC enumerated with the CellSearch system is associated with a relative short survival and their continued presence after the first cycles of therapy indicates a futile therapy in patients with metastatic carcinomas. Detailed characterization of CTC holds the promise to enable the choice of the optimal therapy for the individual patients during the course of the disease. The phenotype, physical and biological properties are however not well understood making it difficult to assess the merit of recent technological advancements to improve upon the capture of CTC or to evaluate their metastatic potential. Here we will discuss the recent advances in the classification of CTC captured by the CellSearch system, the implications of their features and numbers. Latest capture platforms are reviewed and placed in the light of technology improvements needed to detect CTC. Physical properties, phenotype, viability and proliferative potential and means to assess their proliferation and metastatic capacity will be summarized and placed in the context of the latest CTC capture platforms.
Heterogeneity in Circulating Tumor Cells: The Relevance of the Stem-Cell Subset
Cancers, 2019
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...
Pathobiology, 2012
The occurrence of either regional or distant metastases is an indicator of poor prognosis for cancer patients. The mechanism of their formation has not yet been fully uncovered, which limits the possibility of developing new therapeutic strategies. Nevertheless, the discovery of circulating tumor cells (CTCs), which are responsible for tumor dissemination, and cancer stem cells (CSCs), required for tumor growth maintenance, shed light on the metastatic cascade. It seems that CTCs and CSCs are not necessarily separate populations of cancer cells, as CTCs generated in the process of epithelial-mesenchymal transition (EMT) can bear features characteristic of CSCs. This article describes the mechanisms of CTC and CSC formation and characterizes their molecular hallmarks. Moreover, we present different types of EMT occurring in physiological and pathological conditions, and we demonstrate its crucial role in providing CTCs with a CSC phenotype. The article delineates molecular changes ac...
Cancer Research, 2009
Epithelial cancer cells are likely to undergo epithelial-mesenchymal transition (EMT) prior to entering the peripheral circulation. By undergoing EMT, circulating tumor cells (CTCs) lose epithelial markers and may escape detection by conventional methods. Therefore, we conducted a pilot study to investigate mRNA transcripts of EMT-inducing transcription factors (TFs) in tumor cells from the peripheral blood (PB) of patients with primary breast cancer (PBC). PB mononuclear cells were isolated from 52 patients with stages I-III PBC and 30 healthy donors (HDs) and were sequentially depleted of EpCAM 1 cells and CD45 1 leukocytes, henceforth referred to as CD45 2 . The expression levels of EMT-inducing TFs (TWIST1, SNAIL1, SLUG, ZEB1 and FOXC2) in the CD45 2 cells were determined using quantitative real-time polymerase chain reaction. The highest level of expression by the CD45 2 cell fraction of HD was used as ''cutoff'' to determine if samples from patients with PBC overexpressed any EMT-inducing TFs. In total, 15.4% of patients with PBC overexpressed at least one of the EMT-inducing TF transcripts. Overexpression of any EMT-inducing TF transcripts was more likely to be detected in patients with PBC who received neoadjuvant therapies (NAT) than patients who received no NAT (p 5 0.003). Concurrently, CTCs were detected in 7 of 38 (18.4%) patients by CellSearch V R and in 15 of 42 (35.7%) patients by AdnaTest TM . There was no association between the presence of CTCs measured by CellSearch V R or AdnaTest TM . In summary, our results demonstrate that CTCs with EMT phenotype may occur in the peripheral circulation of patients with PBC and that NAT is unable to eliminate CTCs undergoing EMT.
Ex Vivo Expansion of Circulating Tumour Cells (CTCs)
Research Square (Research Square), 2022
Circulating tumour cells (CTCs) are a critical intermediate step in the process of cancer metastasis. The reliability of CTC isolation/puri cation has limited both the potential to report on metastatic progression and the development of CTCs as targets for therapeutic intervention. Here we report a new methodology, which optimises the culture conditions for CTCs using primary cancer cells as a model system. We exploited the known biology that CTCs thrive in hypoxic conditions, with their survival and proliferation being reliant on the activation of hypoxia-inducible factor 1 alpha (HIF-1α). We isolated epithelial-like and quasi-mesenchymal CTC phenotypes from the blood of a cancer patient and successfully cultured these cells for more than eight weeks. The presence of CTC clusters was required to establish and maintain long-term cultures. This novel methodology for the long-term culture of CTCs will aid in the development of downstream applications, including CTC theranostics.