Circulating Tumor Cells: From Bench to Bedside

Balić, Marija; Williams, Anthony; Lin, Hsien-Chung; Datar, Ram H.; Côté, Richard J.

doi:10.1146/annurev-med-050311-163404

Cited by 82 publications

(61 citation statements)

References 73 publications

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“…22 Other studies on both patients and animal models also suggest that increased cell number within tumor emboli is linked to higher metastasis rates and decreased recurrence-free survival. [4][5][6][7][8] Third, the whole tumor cluster may be easily trapped in vessels and form a metastatic focus, as evidenced by the endothelium-coated metastatic nodules in the livers and lungs of VETC 1 tumor-bearing mice. Therefore, the VETC pattern may provide an efficient novel metastasis mode that relies more on vascular pattern than on the migration and invasion activity of cancer cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Yunfei Yuan, 3 Rong-Ping Guo, 3 Wei-Hua Jia, 4 Jing-Ping Yun, 5 Min-Shan Chen, 3 Yaojun Zhang, 3 and…”

mentioning

confidence: 99%

“…3 Nevertheless, studies on both human patients and animal models have shown that the amount of circulating tumor clusters has a greater correlation with metastasis and recurrence-free survival than that of single circulating tumor cells. [4][5][6][7][8] Furthermore, metastasis has been observed in tumors without signs of EMT, [9][10][11] suggesting the potential existence of EMT-independent metastasis mechanisms.…”

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confidence: 99%

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A novel vascular pattern promotes metastasis of hepatocellular carcinoma in an epithelial–mesenchymal transition–independent manner

et al. 2015

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Early metastasis is responsible for frequent relapse and high mortality of hepatocellular carcinoma (HCC), but its underlying mechanisms remain unclear. Epithelial-mesenchymal transition (EMT) has been considered a key event in metastasis. Based on histological examination of serial HCC sections and three-dimensional reconstruction, we found a novel and prevalent vascular pattern, vessels that encapsulated tumor clusters (VETC) and formed cobweb-like networks. The presence of VETC (VETC 1 ) predicted higher metastasis and recurrence rates of HCC. Using clinical samples and mouse xenograft models, we further showed that VETC was composed of functional vessels with blood perfusion and induced by tumor cells at the early stage of HCC. Subsequent investigations revealed that HCC cell-derived angiopoietin-2 was a prerequisite for VETC formation and that the VETC pattern was a critical factor promoting HCC metastasis as knockdown of angiopoietin-2 abolished this vascular pattern and consequently attenuated in vivo tumor metastasis. Interestingly, abrogation of EMT by knockdown of Snail or Slug significantly diminished in vivo metastasis of VETC -xenografts but did not affect that of VETC 1 ones, although silencing of Snail or Slug substantially reduced the in vitro migration of both VETC 1 and VETC -HCC cells. In contrast to human VETC -cases, EMT signatures were rarely observed in VETC 1 cases with metastatic potential. Further analysis revealed that VETC provided an efficient metastasis mode by facilitating the release of whole tumor clusters into the bloodstream. Conclusion: Our findings identify a novel metastasis mechanism that relies on vascular pattern but is independent of EMT, which may provide new targets for antimetastasis therapy and offer a basis for selecting patients who may benefit from certain molecularly targeted drugs. (HEPATOLOGY 2015;62:452-465) See Editorial on Page 343 T he current hypothesis of blood-borne metastasis holds that tumor cells must detach from the primary tumor, invade the extracellular matrix and vascular walls, survive in the circulation, extravasate from the vasculature, and grow at a new site.1,2 Accordingly, epithelial-mesenchymal transition (EMT) has been considered a key event for the epithelial tumor cells to lose cell-cell adhesion, acquire enhanced capacity for migration and invasion, and thereby dissociate from the

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Section: Discussionmentioning

confidence: 99%

“…Yunfei Yuan, 3 Rong-Ping Guo, 3 Wei-Hua Jia, 4 Jing-Ping Yun, 5 Min-Shan Chen, 3 Yaojun Zhang, 3 and…”

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confidence: 99%

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confidence: 99%

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A novel vascular pattern promotes metastasis of hepatocellular carcinoma in an epithelial–mesenchymal transition–independent manner

et al. 2015

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“…Based on this principle, high CTC numbers have been correlated with increased metastasis and decreased time to relapse, which supporting the predictive values on cancer progression, prognosis and survival in several cancers [3]. A meta-analysis of 49 eligible studies enrolling 6,825 breast cancer patients indicated CTC a stable prognostic biomarker at both earlyand metastatic stages [4].…”

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confidence: 75%

Circulating Tumor Cells – Cutting Edge Research?

Mayur-Danny¹

2013

Mod Chem Appl

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“…[1][2][3][4][5][6][7] The classical method for enumerating circulating cells is to draw small peripheral blood (PB) samples from the animals, which are subsequently analyzed with techniques such as flow cytometry, fluorescence microscopy, or more recently with microfluidic devices. [8][9][10][11][12] However, this "ex-vivo" approach is known to be fundamentally problematic, since handling, storage, and enrichment of PB samples have been shown to affect cell viability and behavior.…”

Section: Introductionmentioning

confidence: 99%

Performance of computer vision in vivo flow cytometry with low fluorescence contrast

Markovic¹,

Liu²,

Niedre³

2015

J. Biomed. Opt.

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Abstract. Detection and enumeration of circulating cells in the bloodstream of small animals are important in many areas of preclinical biomedical research, including cancer metastasis, immunology, and reproductive medicine. Optical in vivo flow cytometry (IVFC) represents a class of technologies that allow noninvasive and continuous enumeration of circulating cells without drawing blood samples. We recently developed a technique termed computer vision in vivo flow cytometry (CV-IVFC) that uses a high-sensitivity fluorescence camera and an automated computer vision algorithm to interrogate relatively large circulating blood volumes in the ear of a mouse. We detected circulating cells at concentrations as low as 20 cells∕mL. In the present work, we characterized the performance of CV-IVFC with low-contrast imaging conditions with (1) weak cell fluorescent labeling using cell-simulating fluorescent microspheres with varying brightness and (2) high background tissue autofluorescence by varying autofluorescence properties of optical phantoms. Our analysis indicates that CV-IVFC can robustly track and enumerate circulating cells with at least 50% sensitivity even in conditions with two orders of magnitude degraded contrast than our previous in vivo work. These results support the significant potential utility of CV-IVFC in a wide range of in vivo biological models.

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Circulating Tumor Cells: From Bench to Bedside

Cited by 82 publications

References 73 publications

A novel vascular pattern promotes metastasis of hepatocellular carcinoma in an epithelial–mesenchymal transition–independent manner

A novel vascular pattern promotes metastasis of hepatocellular carcinoma in an epithelial–mesenchymal transition–independent manner

Circulating Tumor Cells – Cutting Edge Research?

Performance of computer vision in vivo flow cytometry with low fluorescence contrast

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