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Hamilton et al. J Cancer Metastasis Treat 2016;2:446-52                             Journal of
           DOI: 10.20517/2394-4722.2016.57
                                                             Cancer Metastasis and Treatment

                                                                                               www.jcmtjournal.com
            Topic: Circulating Tumor Cells: Diagnostics and Clinical Applications               Open Access


           Insights into mechanisms of tumor

           dissemination from circulating tumor cell

           lines of small cell lung cancer



           Gerhard Hamilton, Barbara Rath

           Society for Research on Biology and Treatment of Cancer, A-1160 Vienna, Austria.

           Correspondence to: Dr. Gerhard Hamilton, Society for Research on Biology and Treatment of Cancer, A-1160 Vienna, Austria.
           E-mail: hamilton.srbtc@gmx.org; gerhard.hamilton@meduniwien.ac.at
           How to cite this article: Hamilton G, Rath B. Insights into mechanisms of tumor dissemination from circulating tumor cell lines of small cell lung
           cancer. J Cancer Metastasis Treat 2016;2:446-52.
                                         ABSTRACT

            Article history:              Despite the fact that the majority of cancer patients succumb to metastatic disease, most
            Received: 21-09-2016          aspects of tumor metastasis are not understood in detail at present. Cell biologic steps of
            Accepted: 01-12-2016          dissemination are difficult to characterize in human tumors and research is in large part
            Published: 16-12-2016         confined to cell line and experimental animal studies. Epithelial-mesenchymal transition
                                          (EMT), intravasation of malignant cells, dissemination as circulating tumor cells (CTCs)
            Key words:                    and eventually mesenchymal-epithelial transition (MET) at distal sites are steps believed
            Cancer metastasis,            to be involved in metastasis. Small cell lung cancer (SCLC) is distinguished by early
            small cell lung cancer,       dissemination and excessive numbers of CTCs, which allowed for the ex vivo expansion of
            circulating tumor cells,      six permanent CTC lines taken from relapsed patients. Cells exhibit an epithelial phenotype
            epithelial-mesenchymal transition,  with partial EMT traits and are chemoresistant due to formation of large tumorospheres.
            tumorosphere,                 Since cells may have invaded without undergoing EMT, the role of MET is uncertain. These
            chemotherapy,                 SCLC CTC cell lines seem to represent the metastasis-inducing cancer cells; these are the
            drug resistance               minute subpopulation of CTCs capable of surviving in the circulation and transitioning
                                          to metastases, leading in turn to resistance and failure of therapy. Full characterization of
                                          these lines is expected to provide the markers to find the relevant CTCs among the highly
                                          heterogeneous population observable in the context of tumor recurrence.


           INTRODUCTION                                       the further development of the malignancy. Especially
                                                              in tumor types showing a high frequency of systemic
           Early detection, precise  diagnosis  and monitoring  of   disease, such as small cell lung cancer (SCLC), a small
           the course of disease during therapy are the objective   needle biopsy is procured first to confirm the diagnosis,
           of  individualized care in current oncology.  For  most   and chemotherapy is started without any further
           tumors, a tumor biopsy is costly, painful, or potentially   invasive procedure.  Thus, the opportunity to obtain
                                                                                [1]
           hazardous for the patient and is not performed during   essential information from blood samples, as so-called

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