A microfluidic device for isolation and characterization of transendothelial migrating cancer cells

Cui, Xin; Guo, Weijin; Sun, Yubing; Sun, Baoce; Hu, Shuhuan; Sun, Dong; Lam, Raymond H. W.

doi:10.1063/1.4974012

Cited by 32 publications

(37 citation statements)

References 53 publications

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“…Various factors involved in cancer cell extravasation were investigated, such as CXCL-12 94,95,100 , tumor integrin β1 98 , and TNF-α 97 . Microfluidic devices have also been developed to isolate subpopulations that were able to migrate through confinement 45 and endothelial cells 101 to further investigate intratumor heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…These three cell types have been indicated to promote metastasis to a variety of secondary tumor sites. Therefore, more advanced microfluidic devices began to involve co-cultures with macrophages 89,90 , CAFs [91][92][93] , and endothelial cells [94][95][96][97][98][99][100][101] . One device used macrophages and cancer cells suspended in 2.5 mg mL − 1 collagen (Figure 3a) 90 .…”

Section: Microfluidic Investigation Of Biochemical Signals In Cancer mentioning

confidence: 99%

“…In addition to observing the effect of different factors on extravasation, due to the increasing interest in intra-tumor heterogeneity, a microfluidic device was developed to isolate invasive subsets for analysis (Figure 3f) 101 . The device consisted of a porous membrane with 20 μm thickness separating a top channel layer and bottom collection chambers.…”

Section: Microfluidic Investigation Of Biochemical Signals In Cancer mentioning

confidence: 99%

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A review of microfluidic approaches for investigating cancer extravasation during metastasis

et al. 2018

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Metastases, or migration of cancers, are common and severe cancer complications. Although the 5-year survival rates of primary tumors have greatly improved, those of metastasis remain below 30%, highlighting the importance of investigating specific mechanisms and therapeutic approaches for metastasis. Microfluidic devices have emerged as a powerful platform for drug target identification and drug response screening and allow incorporation of complex interactions in the metastatic microenvironment as well as manipulation of individual factors. In this work, we review microfluidic devices that have been developed to study cancer cell migration and extravasation in response to mechanical (section 'Microfluidic investigation of mechanical factors in cancer cell migration'), biochemical (section 'Microfluidic investigation of biochemical signals in cancer cell invasion'), and cellular (section 'Microfluidic metastasis-on-a-chip models for investigation of cancer extravasation') signals. We highlight the device characteristics, discuss the discoveries enabled by these devices, and offer perspectives on future directions for microfluidic investigations of cancer metastasis, with the ultimate aim of identifying the essential factors for a 'metastasis-on-a-chip' platform to pursue more efficacious treatment approaches for cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Microfluidic Investigation Of Biochemical Signals In Cancer mentioning

confidence: 99%

Section: Microfluidic Investigation Of Biochemical Signals In Cancer mentioning

confidence: 99%

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A review of microfluidic approaches for investigating cancer extravasation during metastasis

et al. 2018

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“…Recently, Cui et al developed a microfluidic device with multiple cell collection microchambers to study the morphology, cytoskeletal structure, and migration of transepithelial-migrated cells with high specificity, so a fully covered epithelial layer is no longer required for migration 117 .…”

Section: Microfluidics-based Methodsmentioning

confidence: 99%

Biomechanics of Collective Cell Migration in Cancer Progression: Experimental and Computational Methods

Spatarelu

Zhang

Nguyen

et al. 2019

ACS Biomater. Sci. Eng.

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Cell migration is essential for regulating many biological processes in physiological or pathological conditions, including embryonic development and cancer invasion. In vitro and in silico studies suggest that collective cell migration is associated with some biomechanical particularities, such as restructuring of extracellular matrix (ECM), stress and force distribution profiles, and reorganization of cytoskeleton. Therefore, the phenomenon could be understood by an in-depth study of cells' behavior determinants, including but not limited to mechanical cues from the environment and from fellow "travelers". This review article aims to cover the recent development of experimental and computational methods for studying the biomechanics of collective cell migration during cancer progression and invasion. We also summarized the tested hypotheses regarding the mechanism underlying collective cell migration enabled by these methods. Together, the paper enables a broad overview on the methods and tools currently available to unravel the biophysical mechanisms pertinent to cell collective migration, as well as providing perspectives on future development towards eventually deciphering the key mechanisms behind the most lethal feature of cancer. I.

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“…Microfluidic devices have served as excellent platforms for similar long-term imaging tasks in mammalian cells (12,13), bacteria (14)(15)(16), and plants (17,18). Indeed, a 'coral-on-a-chip' microfluidic platform was previously developed for bulk reef-building coral microscopy (19).…”

mentioning

confidence: 99%

Live imaging of Aiptasia larvae, a model system for studying coral bleaching, using a simple microfluidic device

Treuren

Brower

Labanieh

et al. 2018

Preprint

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Coral reefs, and their associated diverse ecosystems, are of enormous ecological importance. In recent years, coral health has been severely impacted by environmental stressors brought on by human activity and climate change, threatening the extinction of several major reef ecosystems. Reef damage is mediated by a process called 'coral bleaching' where corals, sea anemones, and other cnidarians lose their photosynthetic algal symbionts (genus Symbiodinium) upon stress induction, resulting in drastically decreased host energy harvest and, ultimately, coral death. The mechanism by which this critical cnidarian-algal symbiosis is lost remains poorly understood. Here, we report 'Traptasia', a simple microfluidic device with multiple traps designed to isolate and image individual live larvae of Aiptasia, a sea anemone model organism, and their algal symbionts over extended time courses. Aiptasia larvae are ∼100 µm in length, deformable, and highly motile, posing particular challenges for long-term imaging. Using a trap design optimized via fluid flow simulations and polymer bead loading tests, we trapped Aiptasia larvae containing algal symbionts and demonstrated stable imaging for >10 hours. We visualized algal migration within Aiptasia larvae and observed algal expulsion under an environmental stressor. To our knowledge, this device is the first to enable live imaging of cnidarian larvae and their algal symbionts and, in further implementation, could provide important insights into the cellular mechanisms of coral bleaching under different environmental stressors. The device is simple to use, requires minimal external equipment and no specialized training to operate, and can easily be adapted to study a variety of large, motile organisms. C oral reefs are remarkably productive ecosystems, supporting approximately 9% of the ocean fish biomass and 25% of oceanic species diversity(1). Reef-building corals depend on an endosymbiotic relationship with dinoflagellate algae (genus Symbiodinium) for survival and productive growth(2, 3), as most corals and other symbiotic cnidarians derive their primary metabolic energy through algal photosynthesis(4). Under environmental and anthropogenic stressors such as rising ocean acidity, pollution, and increasing temperature, the coral-algal symbiotic relationship can break down, resulting in a process known as 'coral bleaching'(1, 5). In this process, photosynthetic algal symbionts are expelled from the coral gastrodermal tissue where they normally reside, resulting in coral discoloration and, if prolonged, host death due to insufficient energy metabolism(5). On a macro-scale, coral bleaching has been implicated as a major cause of rapid worldwide reef deterioration and ecosystem disruption(1). To address this threat, coral-algal symbiosis, in general, and the mechanism of coral bleaching, in particular, must be better understood.While candidate stressors that contribute to coral bleaching are known, the molecular and cellular mechanisms of algal expulsion remain poorly characteriz...

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A microfluidic device for isolation and characterization of transendothelial migrating cancer cells

Cited by 32 publications

References 53 publications

A review of microfluidic approaches for investigating cancer extravasation during metastasis

A review of microfluidic approaches for investigating cancer extravasation during metastasis

Biomechanics of Collective Cell Migration in Cancer Progression: Experimental and Computational Methods

Live imaging of Aiptasia larvae, a model system for studying coral bleaching, using a simple microfluidic device

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