Clusters of circulating tumor cells traverse capillary-sized vessels

Au, Sam H.; Storey, Brian D.; Moore, John C.; Tang, Qin; Chen, Yeng-Long; Javaid, Sarah; Sarioglu, A. Fatih; Sullivan, Ryan J.; Madden, Marissa W.; O’Keefe, Ryan; Haber, Daniel A.; Maheswaran, Shyamala; Langenau, David M.; Stott, Shannon L.; Toner, Mehmet

doi:10.1073/pnas.1524448113

Cited by 383 publications

(365 citation statements)

References 46 publications

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“…One of the possible routes to bypass the capillary circuit could be through arteriovenous anastomoses, which are large circulatory connections between arterial and venous circulation (29). Recently, Au et al (30) showed that clusters of tumor cells, owing to their high deformability, can even traverse capillarysized blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Tumor-derived circulating endothelial cell clusters in colorectal cancer

et al. 2016

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CitationTumor-derived circulating endothelial cell clusters in colorectal cancer. 2016, 8 (345) * Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumorderived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

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Section: Discussionmentioning

confidence: 99%

Tumor-derived circulating endothelial cell clusters in colorectal cancer

et al. 2016

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“…But if not by EMT, then by what alternative physical process might migration become initiated and sustained? Insofar as cell jamming has been reported in murine cancer models in vivo (Haeger et al, 2014), a simple but untested hypothesis cannot be ruled out: (1) at the primary tumor site, migration of a leader cell, together with its followers, through surrounding solid tissues is triggered by the transition of those cells from a solid-like jammed phase to a fluid-like unjammed phase; (2) upon meeting the circulation, forming a CTC and becoming exposed to the destabilizing mechanical effects of blood-borne shear stresses, the CTC stabilizes itself in response by undergoing a transition back to a solid-like jammed phase; and, (3) upon reaching its ultimate metastatic site and unjamming once again (Au et al, 2016), these CTC cells initiate collective cellular invasion into noncancerous solid tissue. The idea that metastasis requires EMT and its inverse, MET, thus compares with the alternative hypothesis that metastasis requires events that are by comparison substantially less drastic -transitions between solid-like ( jammed) and fluid-like (unjammed) phases of the cell layer -during which strong collectivity and an epithelial phenotype is retained throughout.…”

Section: Open Questionsmentioning

confidence: 99%

Collective migration and cell jamming in asthma, cancer and development

Park

Atia

Mitchel

et al. 2016

Journal of Cell Science

133

161

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Collective cellular migration within the epithelial layer impacts upon development, wound healing and cancer invasion, but remains poorly understood. Prevailing conceptual frameworks tend to focus on the isolated role of each particular underlying factor -taken one at a time or at most a few at a time -and thus might not be tailored to describe a cellular collective that embodies a wide palette of physical and molecular interactions that are both strong and complex. To bridge this gap, we shift the spotlight to the emerging concept of cell jamming, which points to only a small set of parameters that govern when a cellular collective might jam and rigidify like a solid, or instead unjam and flow like a fluid. As gateways to cellular migration, the unjamming transition (UJT) and the epithelial-to-mesenchymal transition (EMT) share certain superficial similarities, but their congruence -or lack thereof -remains unclear. In this Commentary, we discuss aspects of cell jamming, its established role in human epithelial cell layers derived from the airways of nonasthmatic and asthmatic donors, and its speculative but emerging roles in development and cancer cell invasion.

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“…3,43) To examine the efficiency of detection of CTC clusters by our method, we prepared cancer cell line tumor spheres (clusters) in vitro. B16…”

Section: Detection Of Cancer Cells and Cancer Clusters Spiked In Bloodmentioning

confidence: 99%

Size-Based Differentiation of Cancer and Normal Cells by a Particle Size Analyzer Assisted by a Cell-Recognition PC Software

Shashni

Ariyasu

Takeda

et al. 2018

Biological & Pharmaceutical Bulletin

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SummaryDetection of anomalous cells such as cancer cells from normal blood cells has the potential to contribute greatly to cancer diagnosis and therapy. Conventional methods for the detection of cancer cells are usually tedious and cumbersome. Herein, we report on the use of a particle size analyzer for the convenient size-based differentiation of cancer cells from normal cells. Measurements made using a particle size analyzer revealed that size parameters for cancer cells are significantly greater (e.g., inner diameter and width) than the corresponding values for normal cells (white blood cells (WBC), lymphocytes and splenocytes), with no significant difference in shape parameters (e.g., circularity and convexity). The inner diameter of many cancer cell lines is greater than 10 μm, in contrast to normal cells. For the detection of WBC having similar size to that of cancer cells, we developed a PC software "Cancer Cell Finder" that differentiates them from cancer cells based on brightness inflection points on a cell surface. Furthermore, the aforementioned method was validated for cancer cell/clusters detection in spiked mouse blood samples (a B16 melanoma mouse xenograft model) and circulating tumor cell cluster-like particles in the cat and dog (diagnosed with cancer) blood samples. These results provide insights into the possible applicability of the use of a particle size analyzer in conjunction with PC software for the convenient detection of cancer cells in experimental and clinical samples for theranostics.

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Clusters of circulating tumor cells traverse capillary-sized vessels

Cited by 383 publications

References 46 publications

Tumor-derived circulating endothelial cell clusters in colorectal cancer

Tumor-derived circulating endothelial cell clusters in colorectal cancer

Collective migration and cell jamming in asthma, cancer and development

Size-Based Differentiation of Cancer and Normal Cells by a Particle Size Analyzer Assisted by a Cell-Recognition PC Software

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