The viable circulating tumor cells with cancer stem cells feature, where is the way out?

Abstract

With cancer stem cells (CSCs) became the research hotspot, emerging studies attempt to reveal the functions of these special subsets in tumorigenesis. Although various approaches have been used in CSCs researches, only a few could really reflect or simulate the microenvironment in vivo. At present, CSCs theories are still difficult to apply for clinical remedy because CSCs subpopulations are always hard to identify and trace. Thus an ideal approach for clinicians and researchers is urgently needed. Circulating tumor cells (CTCs), as the method of noninvasive-liquid biopsy, could be detected in the peripheral blood (PB) from many tumors and even could be treated as procurators for CSCs deeper researches from patient-derived sample. However, CTCs, as a diagnostic marker, also raise much controversy over theirs clinical value. Mechanisms causing CTCs to shed from the tumor have not been fully characterized, thus it is unclear whether CTCs represent the entire makeup of cancer cells in the tumor or only a subset. The heterogeneity of CTCs also caused different clinical outcomes. To overcome these unsolved problems, recently, CTC researches are not just depend on enumerations, whereas those CTC subsets that could expand in vitro may play a pivotal role in the metastatic cascade. Here, we retrospect the CTC developmental history and discourse upon the enrichment of viable CTCs in functional assays, probe the further avenue at the crossroad.

Novel molecular insights and new therapeutic strategies in osteosarcoma

“…CTCs are a heterogeneous and rare population of cells in the blood, which despite the tremendous advances in recent years, have not been adequately characterized because of their heterogeneity and dynamism [ 140 , 141 ]. The mechanisms that release the CTCs from the tumor are not completely determined It is not known, therefore, whether the CTCs represent only represent a subset of cancer cells makeup in the tumor, or are involved in entire [ 142 ]. A question that requires more studies to be clarified.…”

“…Overall, it should be taken into consideration that a reduction in the CTC does not adequately provide the exacted insight into the biology of the tumor and therapeutic responses, whereas rare CTSCs remained unaffected, indicating the importance of identifying CTSCs for providing treatment strategies [ 141 , 153 ]. CTCs may be only linked to tumor burden or represent the leakiness of tumor-related vasculature [ 142 , 154 ].…”

The Role of Circulating Tumor Cells in the Metastatic Cascade: Biology, Technical Challenges, and Clinical Relevance

“…Moreover, epithelial cell adhesion molecule (EpCAM), which is an epithelial marker, has been detected in CTSCs with cytogenetic abnormalities [12]. Like CSCs, CTSCs go through a dynamic conversion upon exposure to environmental stress [13]. EMT, which contributes to tumor cell dissemination, also promotes cancer cell ability to self-renew [2,14].…”

“…It is not clear whether CTCs are representative of the whole tumor cell population or, similarly to CSCs, are a rare subpopulation [13]. Moreover, some migrating CSCs might give rise to CTCs that form metastases [11].…”

Effects of salinomycin and niclosamide on small cell lung cancer and small cell lung cancer circulating tumor cell lines

“…Metastasis-initiating capabilities of CTCs based on stemness properties are difficult to detect since CTCs show extensive heterogeneity and only an extremely small fraction of these cells is able to establish secondary lesions [32,33]. In vitro expansion of relevant CTCs has been reported for only a limited number of tumors and cell lines so far [34].…”