Abstract
Epigenetics contributes to molecular mechanisms leading to tumor cell transformation and systemic progression of cancer. However, the dynamics of epigenetic remodeling during metastasis remains unexplored. In this context, circulating tumor cells (CTCs) might enable a direct insight into epigenetic mechanisms relevant for metastasis by providing direct access to systemic cancer. CTCs can be used as prognostic markers in cancer patients and are regarded as potential metastatic precursor cells. However, despite substantial technical progress, the detection and molecular characterization of CTCs remain challenging, in particular the analysis of DNA methylation. As recent studies have started to address the epigenetic state of CTCs, we discuss here the potential of such investigations to elucidate mechanisms of metastasis and to develop tumor biomarkers.
Highlights
Metastasis is a multi-step process involving tumor cell migration, intravasation, survival in the blood stream, extravasation at a secondary site, and colonization
Tumor cells that have left the primary tumor or metastases and that can be found in the circulation of patients are an important source of information about this process
We review in detail the existing literature on DNA methylation in circulating tumor cells (CTCs), discuss the major technical challenges for their epigenetic analysis, and provide our perspective on the potential contained in a deeper epigenetic characterization of CTCs
Summary
Metastasis is a multi-step process involving tumor cell migration, intravasation, survival in the blood stream, extravasation at a secondary site, and colonization. Systemic disease is driven by cells that have successfully accomplished at least some steps of the metastatic cascade Compared to their primary tumors, these cells have usually accumulated additional genetic and phenotypic alterations as a result of ongoing genetic instability and the different selective pressures experienced in the various micro-environments [2]. Tumor cells that have left the primary tumor or metastases and that can be found in the circulation of patients (circulating tumor cells, CTCs) are an important source of information about this process In addition to their heuristic value for understanding fundamental aspects of tumor progression, these cells have been proven to be clinically relevant, and their molecular characterization is acknowledged as an opportunity for real-time monitoring of the disease progression and of the molecular evolution of metastatic systemic disease [3,4]. We review in detail the existing literature on DNA methylation in CTCs, discuss the major technical challenges for their epigenetic analysis, and provide our perspective on the potential contained in a deeper epigenetic characterization of CTCs
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