Clinical and biological significance of circulating tumor cells in cancer

Masuda, Takaaki; Hayashi, Naoki; Iguchi, Tomohiro; Ito, Shuhei; Eguchi, Hidetoshi; Mimori, Koshi

doi:10.1016/j.molonc.2016.01.010

Cited by 122 publications

(125 citation statements)

References 96 publications

(137 reference statements)

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“…Silencing EMT-related genes is an attractive therapeutic approach for improving treatment outcomes [25–27]. The present study found that HINT2 downregulation promotes CRC cell migration and invasion by enhancing the ZEB1-mediated EMT response through HIF-2α.…”

Section: Discussionsupporting

confidence: 52%

HINT2 downregulation promotes colorectal carcinoma migration and metastasis

Cai

Wang

et al. 2017

Oncotarget

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Histidine triad nucleotide-binding 2 (HINT2), a member of the histidine triad proteins family, sensitizes cells to apoptosis in hepatocellular carcinoma. Here, we showed that HINT2 expression is lower in primary colorectal cancer (CRC) and metastasis tissues than in normal colorectal tissues, and that HINT2 abundance is inversely correlated with CRC tumor stage. Treating CRC cells with 5-aza-2′-deoxycytidine, a demethylating agent, upregulated HINT2, suggesting HINT2 downregulation is caused by methylation of the gene promoter. HINT2 downregulation increased tumor migration and invasion in vitro, promoted CRC cell metastasis in vivo, and increased expression of epithelial-to-mesenchymal transition (EMT) markers. Furthermore, HINT2 downregulation depended on hypoxia inducible factor (HIF)-2α-mediated transcriptional activation of zinc finger E-box-binding homeobox 1 (ZEB1). These results suggest that HINT2 downregulation promotes HIF-2α expression, which induces EMT and enhances CRC cell migration and invasion. HINT2 may thus a useful clinical indicator of CRC progression and metastasis risk.

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Section: Discussionsupporting

confidence: 52%

HINT2 downregulation promotes colorectal carcinoma migration and metastasis

Cai

Wang

et al. 2017

Oncotarget

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“…Up to now, CTCs have been well studied and are currently being used in the clinical setting10. However, there are controversial results about the effectiveness of different treatments to reduce CTCs.…”

mentioning

confidence: 99%

Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis

Yan

Cui

Chen

et al. 2017

Sci Rep

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Whether circulating tumor cells (CTCs) can be used as an indicator of treatment response in breast cancer (BC) needs to be clarified. We addressed this issue by a meta-analysis. PubMed, EMBase and Cochrane library databases were searched in June 2016. Effect measures were estimated as pooled risk ratio (RR), odds ratio (OR) or mean difference by fixed- or random-effect models, according to heterogeneity of included studies. In total, 50 studies with 6712 patients were recruited. Overall analysis showed that there was a significant reduction of CTC-positive rate (RR = 0.68, 95% CI: 0.61–0.76, P < 0.00001) after treatment. Subgroup analyses revealed that neoadjuvant treatment, adjuvant treatment, metastatic treatment or combination therapy could reduce the CTC-positive rate, but surgery could not; moreover, the reduction was only found in HER2+ or HER2- patients but not in the triple-negative ones. Reduction of CTC-positive rate was associated with lower probability of disease progression (OR = 0.54, 95% CI: 0.33–0.89, P = 0.01) and longer overall survival period (mean difference = 11.61 months, 95% CI: 8.63–14.59, P < 0.00001) as well as longer progression-free survival period (mean difference = 5.07 months, 95% CI: 2.70–7.44, P < 0.0001). These results demonstrate that CTC status can serve as an indicator to monitor the effectiveness of treatments and guide subsequent therapies in BC.

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“…Significant efforts have been made to isolate CTCs for early detection and examination of their dynamic temporal changes for prognosis, disease management and surveillance . CTCs can be biochemically, genetically and biophysically characterized . Biochemically, a cell is a CTCs if it co‐expresses the epithelial cell adhesion molecule (EpCAM) and cytokeratin (CKs – e.g .…”

Section: Introductionmentioning

confidence: 99%

Highlighting the uniqueness in dielectrophoretic enrichment of circulating tumor cells

et al. 2019

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Circulating tumor cells (CTCs) play an essential role in the metastasis of tumors, and thus can serve as a valuable prognostic factor for malignant diseases. As a result, the ability to isolate and characterize CTCs is essential. This review underlines the potential of dielectrophoresis for CTCs enrichment. It begins by summarizing the key performance parameters and challenges of CTCs isolation using microfluidics. The two main categories of CTCs enrichment—affinity‐based and label‐free methods—are analysed, emphasising the advantages and disadvantages of each as well as their clinical potential. While the main argument in favour of affinity‐based methods is the strong specificity of CTCs isolation, the major advantage of the label‐free technologies is in preserving the integrity of the cellular membrane, an essential requirement for downstream characterization. Moving forward, we try to answer the main question: “What makes dielectrophoresis a method of choice in CTCs isolation?” The uniqueness of dielectrophoretic CTCs enrichment resides in coupling the specificity of the isolation process with the conservation of the membrane surface. The specificity of the dielectrophoretic method stems from the differences in the dielectric properties between CTCs and other cells in the blood: the capacitances of the malignantly transformed cellular membranes of CTCs differ from those of other cells. Examples of dielectrophoretic devices are described and their performance evaluated. Critical requirements for using dielectrophoresis to isolate CTCs are highlighted. Finally, we consider that DEP has the potential of becoming a cytometric method for large‐scale sorting and characterization of cells.

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Clinical and biological significance of circulating tumor cells in cancer

Cited by 122 publications

References 96 publications

HINT2 downregulation promotes colorectal carcinoma migration and metastasis

HINT2 downregulation promotes colorectal carcinoma migration and metastasis

Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis

Highlighting the uniqueness in dielectrophoretic enrichment of circulating tumor cells

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