Tumor relapse and metastasis are the primary causes of poor survival rates in patients with advanced cancer despite successful resection or chemotherapeutic treatment. A primary cause of relapse and metastasis is the persistence of cancer stem cells (CSCs), which are highly resistant to chemotherapy. Although highly efficacious drugs suppressing several subpopulations of CSCs in various tissue-specific cancers are available, recurrence is still common in patients. To find more suitable therapy for relapse, the mechanisms underlying metastasis and drug-resistance associated with relapse-initiating CSCs need to be identified. Recent studies in circulating tumor cells (CTCs) of some cancer patients manifest phenotypes of both CSCs and epithelial-mesenchymal transition (EMT). These patients are unresponsive to standard chemotherapies and have low progression free survival, suggesting that EMT-positive CTCs are related to co-occur with or transform into relapse-initiating CSCs. Furthermore, EMT programming in cancer cells enables in the remodeling of extracellular matrix to break the dormancy of relapse-initiating CSCs. In this review, we extensively discuss the association of the EMT program with CTCs and CSCs to characterize a subpopulation of patients prone to relapses. Identifying the mechanisms by which EMT-transformed CTCs and CSCs initiate relapse could facilitate the development of new or enhanced personalized therapeutic regimens.

To date, no specific marker exists for the detection of circulating tumor cell from different types of sarcomas, though tools are available for detection of circulating tumor cell (CTC) in peripheral blood of cancer patients for epithelial cancers. Here we report cell-surface vimentin (CSV) as an exclusive marker on sarcoma CTC regardless of the tissue origin of the sarcoma as detected by a novel monoclonal antibody. Utilizing CSV as a probe we isolated and enumerated sarcoma CTC with high sensitivity and specificity from the blood of patients bearing different types of sarcoma, validating their phenotype by single cell genomic amplification, mutation detection and fluorescence in situ hybridization. Our results establish the first universal and specific CTC marker described for enumerating CTC from different types of sarcoma, thereby providing a key prognosis tool to monitor cancer metastasis and relapse.

Purpose This study aimed to detect cell-surface vimentin (CSV) on the surface of epithelial-mesenchymal transitioned (EMT) circulating tumor cells (CTCs) from blood of patients with epithelial cancers. Experimental Design In this study, 101 patients undergoing post-surgery adjuvant chemotherapy for metastatic colon cancer were recruited. EMT CTCs were detected from blood of patients using 84-1 monoclonal antibody against CSV as a marker. EMT CTCs isolated were characterized further using EMT-specific markers, fluorescent in situ hybridization and single cell mutation analysis. Results Using 84-1 antibody, we detected CSV exclusively on EMT CTCs from a variety of tumor types but not in the surrounding normal cells in the blood. The antibody exhibited very high specificity and sensitivity towards different epithelial cancer cells. With this antibody, we detected and enumerated EMT CTCs from patients. From our observations, we defined a cutoff of < five or ≥ five EMT CTCs as optimal threshold with respect to therapeutic response using ROC curves. Using this defined threshold, the presence of ≥ five EMT CTCs was associated with progressive disease, while patients with less than five EMT CTCs showed therapeutic response. Conclusion Taken together, number of EMT CTCs detected correlated with the therapeutic outcome of the disease. These results establish cell-surface vimentin as a universal marker for EMT CTCs from a wide variety of tumor types and thus provide the foundation for emerging CTC detection technologies and for studying the molecular regulation of these EMT CTCs.

For decades, immortal cancer cell lines have constituted an accessible, easily usable set of biological models to investigate cancer biology and explore the potential efficacy of anticancer drugs. However, numerous studies suggest that these cell lines poorly represent the diversity, heterogeneity and drug-resistant tumors occurring in patients. The derivation and short -term culture of primary cells from solid tumors have thus gained significant importance in personalized cancer therapy. This review focuses our current understanding and the pros and cons of different methods for primary tumor cell culture. Furthermore, various culture matrices like biomimetic scaffolds, chemically defined media supplemented with essential nutrients have been prepared for different tissues. These well characterized primary tumor cells redefine cancer therapies with high translational relevance.