Circulating Tumor Cells, Enumeration and Beyond

Hou, Jian Mei; Krebs, Matthew; Ward, Timothy H; Morris, Karen; Szczepaniak-Sloane, Robert; Blackhall, Fiona; Dive, Caroline

doi:10.3390/cancers2021236

Cited by 47 publications

(42 citation statements)

References 51 publications

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“…CTC counts in peripheral blood prior treatment can independently predict the early recurrence in patients with cancer (3,4). Overall survival in patients with stage III and IV non-small cell lung cancer (NSCLC) was significantly longer (8.1 months vs. 4.3 months) in patients with fewer than 5 CTCs compared to those with five or more CTCs before chemotherapy (5).…”

Section: Abstract Background: Detection Of Circulating Tumour Cells mentioning

confidence: 99%

Detection of Circulating Tumour Cells and Survival of Patients with Non-Small Cell Lung Cancer

Chudasama

Barr

Beeson

et al. 2017

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Section: Abstract Background: Detection Of Circulating Tumour Cells mentioning

confidence: 99%

Detection of Circulating Tumour Cells and Survival of Patients with Non-Small Cell Lung Cancer

Chudasama

Barr

Beeson

et al. 2017

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“…Moreover, using the Food and Drug Administration's approved CellSearch platform, the CTC number is a prognostic biomarker in metastatic breast, prostate, and colorectal cancer patients. [7][8][9][10][11] The phenomenon of "partial" or "incomplete" EMT is also purported, in which metastasizing cells adopt some mesenchymal features (eg, expression of vimentin and neural cadherin) but retain some epithelial characteristics (eg, cytokeratin and membrane E-cadherin). 12 An alternative model for metastasis involving tumor cell co-operativity has also been postulated based on a rodent model that demonstrated mesenchymal cells provided invasive capability to allow "passenger" noninvasive epithelial cells access to the blood stream where they survived and were responsible for metastasis.…”

mentioning

confidence: 99%

Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer

Hou

Krebs

Ward

et al. 2011

The American Journal of Pathology

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391

369

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Circulating tumor cell (CTC) number in metastatic cancer patients yields prognostic information consistent with enhanced cell migration and invasion via loss of adhesion, a feature of epithelial-to-mesenchymal transition (EMT). Tumor cells also invade via collective migration with maintained cell-cell contacts and consistent with this is the circulating tumor microemboli (CTM; contiguous groups of tumor cells) that are observed in metastatic cancer patients. Using a blood filtration approach, we examined markers of EMT (cytokeratins, E-cadherin, vimentin, neural cadherin) and prevalence of apoptosis in CTCs and CTM to explore likely mechanism(s) of invasion in lung cancer patients and address the hypothesis that cells within CTM have a survival advantage. Intra-patient and inter-patient heterogeneity was observed for EMT markers in CTCs and CTM. Vimentin was only expressed in some CTCs, but in the majority of cells within CTM; E-cadherin expression was lost, cytoplasmic or nuclear, and rarely expressed at the surface of the cells within CTM. A subpopulation of CTCs was apoptotic, but apoptosis was absent within CTM. This pilot study suggests that EMT is not prosecuted homo- Metastasis usually portends a dismal prognosis for cancer patients and effective therapeutic intervention in the metastatic process remains elusive. This is the case despite decades of research after Paget's "seed and soil" hypothesis in 1889 to explain why primary tumors within one particular organ give rise to secondary tumors at nonrandom sites 1 and Ewing's suggestion in 1929 that mechanical factors associated with the anatomy of human vasculature also determine the final destination of metastasizing tumor cells. 2 It is now apparent that tumor cell invasion and formation of distant metastasis can progress via three major routes: i) via the bloodstream, ii) via lymphatic vessels, and iii) via transcoelomic spread into the pleural, pericardial, and abdominal cavities. 3 The hematogenous system is thought to be the primary and most common route for the formation of distant metastases. Disseminating tumor cells can also circulate to and lie dormant in the bone marrow, potentially for a number of years, and then re-enter the bloodstream en route to secondary metastatic sites. 4 According to the widely espoused epithelial-to-mesenchymal transition (EMT) paradigm, suggested by some as essential for metastasis, 5,6 invading mesenchymal tumor cells lose cell-cell adhesion. Consistent with this concept, there are increasing reports enumerating individual circulating tumor cells (CTCs) in cancer patients' blood samples. Moreover, using the Food and Drug Administration's approved CellSearch platform, the CTC number is a prognostic biomarker in metastatic breast,

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“…These data can be further processed from the two-dimensional array to an one-dimensional profile, if desired. By assigning a numerical value of 0 to void bins and a value of 1 to occupied bins, the representative value for each bin address (1)(2)(3)(4)(5)(6)(7)(8) can be calculated by reporting the mean value of each specific bin address across all of the chambers used. This concept is shown as the "Event Distribution" in Figure 5b and is sufficient to visualize the relative load of multi-cellular clusters present in the original blood sample.…”

Section: Examination Of the Clustering Potential Inherent In Specificmentioning

confidence: 99%

“…The presence of circulating tumour cells (CTCs) in the blood of a patient, as found in most forms of epithelial cancer [1][2][3][4][5] , has been identified as a reliable indicator of the prognosis of various cancer types. More recently, the propensity of CTCs to occur in multicellular clusters (sometimes referred to as circulating tumour microemboli or CTM) has been observed by a number of groups using a number of technologies.…”

Section: Introductionmentioning

confidence: 99%

Cluster size distribution of cancer cells in blood using stopped-flow centrifugation along scale-matched gaps of a radially inclined rail

et al. 2015

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There is increasing evidence that, in addition to their presence, the propensity of circulating tumour cells to form multi-cellular clusters bears significant information about both cellular resistance to chemotherapy and overall prognosis. We present a novel two-stage, stopped-flow, continuous centrifugal sedimentation strategy to measure the size distributions of events (defined here as cells or clusters thereof) in a blood sample. After off-chip removal of red blood cells, healthy white blood cells are sequestered by negative-immunocapture. The purified events are then resolved along a radially inclined rail featuring a series of gaps with increasing width, each connected to a designated outer collection bin. The isolation of candidate events independent of targetspecific epitopes is successfully demonstrated for HL60 (EpCAM positive) and sk-mel28 (EpCAM negative) cells using identical protocols and reagents. The propensity to form clusters was quantified for a number of cell lines, showing a negligible, moderate or elevated tendency towards cluster formation. We show that the occupancy distribution of the collection bins closely correlates with the range of cluster sizes intrinsic to the specific cell line.

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Circulating Tumor Cells, Enumeration and Beyond

Cited by 47 publications

References 51 publications

Detection of Circulating Tumour Cells and Survival of Patients with Non-Small Cell Lung Cancer

Detection of Circulating Tumour Cells and Survival of Patients with Non-Small Cell Lung Cancer

Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer

Cluster size distribution of cancer cells in blood using stopped-flow centrifugation along scale-matched gaps of a radially inclined rail

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