Quantification of Malignant Breast Cancer Cell MDA-MB-231 Transmigration Across Brain and Lung Microvascular Endothelium

Fan, Jie; Fu, Bingmei M.

doi:10.1007/s10439-015-1517-y

Cited by 37 publications

(62 citation statements)

References 62 publications

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“…The endothelial GCX plays a significant role as a barrier between the endothelium and circulating cells present in the blood stream, including cancer cells . The importance of the endothelial GCX in enabling EC adhesiveness to cancer and other types of circulating cells, primarily when its HS component is shed or in the presence of heparinase enzyme that specifically degrades HS, has been well established (Table ) . Regulation of EC adhesiveness by endothelial GCX components such as CS and HA has also been demonstrated (Table ) .…”

Section: Resultsmentioning

confidence: 99%

“…To date, only a few cell mechanism studies have explored how HS, CS, HA, and SA regulate homing of cells, particularly white blood cells and cancer cells, from vessel circulation to the endothelium surface . Selected reports are summarized in Table , which shows that the majority of investigations have been performed in the context of white blood cells and inflammation, and more work is required in the cancer milieu to address metastasis . The white blood cell studies inform our understanding of GCX‐mediated EC adhesiveness to cancer cells, because cancer cells utilize inflammation mechanisms to metastasize and inflammatory agonists are known to cause endothelial GCX shedding that can expose endothelium to circulating cell adhesion.…”

Section: Introductionmentioning

confidence: 99%

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Metastatic cancer cell attachment to endothelium is promoted by endothelial glycocalyx sialic acid degradation

et al. 2019

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While it is known that cancer cell interactions with vascular endothelial cells (ECs) drive metastatic cancer cell extravasation from blood vessels into secondary tumor sites, the mechanisms of action are still poorly understood. Here, we tested the hypothesis that neuraminidase‐induced degradation of EC surface glycocalyx (GCX), particularly the sialic acid (SA) residue components of the GCX, will substantially increase metastatic cancer cell attachment to ECs. To our knowledge, our study is the first to isolate the role of GCX SA residues in cancer cell attachment to the endothelium, which were found to be differentially affected by the presence of neuraminidase and to indeed regulate metastatic cancer cell homing to ECs. We hope that this work will eventually translate to identification of EC GCX‐based cancer markers that can be therapeutically targeted to hinder the progression of metastasis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metastatic cancer cell attachment to endothelium is promoted by endothelial glycocalyx sialic acid degradation

et al. 2019

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“…For a tumor cell transmigration of the endothelial monolayer, it was observed clearly that there are three states it has to experience: adhesion, transmigrating and transmigrated, as shown in Fig. 1 (Fan and Fu 2015). By using confocal microscopy (Fan and Fu 2015), we have observed the transmigration of a malignant breast tumor cell through the endothelial monolayers, as shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

“…1 (Fan and Fu 2015). By using confocal microscopy (Fan and Fu 2015), we have observed the transmigration of a malignant breast tumor cell through the endothelial monolayers, as shown in Fig. 2.…”

Section: Introductionmentioning

confidence: 99%

Numerical simulation of a single cell passing through a narrow slit

Liu

Chen

et al. 2016

Biomech Model Mechanobiol

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The narrow slit between endothelial cells that line the microvessel wall is the principal pathway for tumor cell extravasation to the surrounding tissue. To understand this crucial step for tumor hematogenous metastasis, we used dissipative particle dynamics method to investigate an individual cell passing through a narrow slit numerically. The cell membrane was simulated by a spring-based network model which can separate the internal cytoplasm and surrounding fluid. The effects of the cell elasticity, cell shape, nucleus and slit size on the cell transmigration through the slit were investigated. Under a fixed driving force, the cell with higher elasticity can be elongated more and pass faster through the slit. When the slit width decreases to 2/3 of the cell diameter, the spherical cell becomes jammed despite reducing its elasticity modulus by 10 times. However, transforming the cell from a spherical to ellipsoidal shape and increasing the cell surface area by merely 9.3% can enable the cell to pass through the narrow slit. Therefore, the cell shape and surface area increase play a more important role than the cell elasticity in cell passing through the narrow slit. In addition, the simulation results indicate that the cell migration velocity decreases during entrance but increases during exit of the slit, which is qualitatively in agreement with the experimental observation.

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“…It is important to note that this assay is only measuring the permeability of FITC-avidin and as such, could return different results for the permeability of molecules of different sizes or charges; or for different cell types transmigrating across the barrier. Use of the JAnaP with other local permeability assays for different molecules [63] or live cell imaging for cell transmigration [5,[64][65][66] could, therefore, provide additional insights into the effects of junction phenotypes. This is especially of interest to further study the differences in function between punctate and perpendicular junctions.…”

Section: Discussionmentioning

confidence: 99%

Quantitatively relating brain endothelial cell–cell junction phenotype to global and local barrier properties under varied culture conditions via the Junction Analyzer Program

Gray

Jung

Inglut

et al. 2020

Fluids Barriers CNS

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Background: The endothelial cell-cell junctions of the blood-brain barrier (BBB) play a pivotal role in the barrier's function. Altered cell-cell junctions can lead to barrier dysfunction and have been implicated in several diseases. Despite this, the driving forces regulating junctional protein presentation remain relatively understudied, largely due to the lack of efficient techniques to quantify their presentation at sites of cell-cell adhesion. Here, we used our novel Junction Analyzer Program (JAnaP) to quantify junction phenotype (i.e., continuous, punctate, or perpendicular) in response to various substrate compositions, cell culture times, and cAMP treatments in human brain microvascular endothelial cells (HBMECs). We then quantitatively correlated junction presentation with barrier permeability on both a "global" and "local" scale. Methods:We cultured HBMECs on collagen I, fibronectin, collagen IV, laminin, fibronectin/collagen IV/laminin, or hyaluronic acid/gelatin for 2, 4, and 7 days with varying cAMP treatment schedules. Images of immunostained ZO-1, VE-cadherin, and claudin-5 were analyzed using the JAnaP to calculate the percent of the cell perimeter presenting continuous, punctate, or perpendicular junctions. Transwell permeability assays and resistance measurements were used to measure bulk ("global") barrier properties, and a "local" permeability assay was used to correlate junction presentation proximal to permeable monolayer regions.Results: Substrate composition was found to play little role in junction presentation, while cAMP supplements significantly increased the continuous junction architecture. Increased culture time required increased cAMP treatment time to reach similar ZO-1 and VE-cadherin coverage observed with shorter culture, though longer cultures were required for claudin-5 presentation. Prolonged cAMP treatment (6 days) disrupted junction integrity for all three junction proteins. Transwell permeability and TEER assays showed no correlation with junction phenotype, but a local permeability assay revealed a correlation between the number of discontinuous and no junction regions with barrier penetration. Conclusions:These results suggest that cAMP signaling influences HBMEC junction architecture more than matrix composition. Our studies emphasized the need for local barrier measurement to mechanistically understand the role of junction phenotype and supported previous results that continuous junctions are indicative of a more mature/ © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material...

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Quantification of Malignant Breast Cancer Cell MDA-MB-231 Transmigration Across Brain and Lung Microvascular Endothelium

Cited by 37 publications

References 62 publications

Metastatic cancer cell attachment to endothelium is promoted by endothelial glycocalyx sialic acid degradation

Metastatic cancer cell attachment to endothelium is promoted by endothelial glycocalyx sialic acid degradation

Numerical simulation of a single cell passing through a narrow slit

Quantitatively relating brain endothelial cell–cell junction phenotype to global and local barrier properties under varied culture conditions via the Junction Analyzer Program

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