Author : Leyla Kermanshah
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (133 download)
Book Synopsis Isolation, Detection and Functional Characterization of Circulating Tumor Cells Using Microfluidic-based Technologies by : Leyla Kermanshah
Download or read book Isolation, Detection and Functional Characterization of Circulating Tumor Cells Using Microfluidic-based Technologies written by Leyla Kermanshah and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Primary tumors shed thousands of cells into blood circulation every day. These circulating tumor cells (CTCs) play a key role in metastasis. The application of CTCs, regarded as a real-time, non-invasive and cost-effective "liquid biopsy", has drawn much attention in the last two decades. However, their application in clinical practice has been limited due to their extreme rarity and heterogeneity. Highly specialized technologies have been developed to address these challenges. So far, the majority of technologies have focused on separating CTCs from a background of millions of blood cells with high purity and sensitivity. Despite the technological advancement in CTC enrichment, the clinical relevance of these cells is still controversial. In-depth characterization is therefore needed to elucidate their functionality in the metastatic cascade. The principal aim of this thesis is to characterize heterogeneous populations of CTCs, sorting them into subpopulations and assessing the CTCs for aggressive phenotypes. In this thesis, specialized microfluidic-based technologies are used for isolating CTCs and profiling their phenotypes according to a surface marker expression. We describe a two-dimensional separation approach that separates phenotypically-distinct subpopulations of cancer cells. Profiling CTCs based on an epithelial marker enabled us to identify CTCs that have undergone the epithelial to mesenchymal transition (EMT). The EMT-transformed cells exhibited greater invasive phenotypes, as confirmed by an in vitro collagen uptake assay. Using magnetic ranking cytometry (MagRC), a new technology designed for profiling rare cells, we successfully obtained phenotypic profiles from cancer cells and xenograft CTCs. To investigate metastatic phenotypes of CTCs, CTCs from mice bearing prostate cancer xenografts with different levels of aggressiveness were analysed by MagRC. Real-time monitoring of dynamic changes in CTC phenotypes during cancer progression and a course of chemotherapy gave us insights into tumor evolution and treatment efficiency. Metastatic xenografts showed a heterogeneous population of CTCs with epithelial-mesenchymal plasticity. A decrease in heterogeneity followed by a reduction in metastasis incidence was observed after a course of chemotherapy administered to highly metastatic xenografts. Phenotypic profiling of CTCs can potentially be used for cancer prognostic profiling and therapeutic selection.