Establishment and application of a dynamic tumor-vessel microsystem for studying different stages of tumor metastasis and evaluating anti-tumor drugs

Jing, Bolin; Luo, Yong; Lin, Baiquan; Li, Jianjun; Wang, Zhuo A.; Du, Yuguang

doi:10.1039/c9ra02069a

Cited by 18 publications

(17 citation statements)

References 47 publications

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“…To determine whether paCOS with F A 0.46 could suppress proliferation of liver tumor cells, the dynamic tumor-vessel microfluidic model for proliferation of tumor cells was employed [13]. The inhibitory effects of paCOS at different concentrations on the proliferation of HepG2 cells were shown in Figure 2A.…”

Section: Resultsmentioning

confidence: 99%

“…Here, paCOS might also inhibit the intravasation of liver tumor cells by interfering with the activity of MMP-9 The inhibitory effect of paCOS on the intravasation of HepG2 cells was stronger than that on invasion of HepG2 cells (Figure 4 and Figure S3). These results suggested that endothelial cells with “blood flow” may be critical for the efficacy of paCOS on cancer metastasis, and functional vasculature and interstitial fluid flow may have major influence on drug transport [13].…”

Section: Discussionmentioning

confidence: 99%

“…Chen et al developed a microfluidic platform to mimic the physiological microenvironment of solid tumors with multicellular tumor spheroids for screening anticancer drugs [12]. We have developed a dynamic tumor-vessel microfluidic device that enabled co-culture tumor cells and endothelial cells at physiological relevant luminal flow rates, which could reproduce the different phases of cancer metastasis individually [13].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Liver Tumor Cell Metastasis by Partially Acetylated Chitosan Oligosaccharide on A Tumor-Vessel Microsystem

et al. 2019

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Chitooligosaccharides (COS), the only cationic oligosaccharide in nature, have been demonstrated to have anti-tumor activity. However, the inhibitory effects of COS on different stages of tumor metastasis are still unknown, and it is not clear what stage(s) of tumor metastasis COS targeted. To study the inhibitory effects of a new partially acetylated chitooligosaccharide (paCOS) with fraction of acetylation (FA) 0.46 on each phase of liver cancer cell metastasis, a dynamic tumor-vessel microsystem undergoing physiological flow was leveraged. paCOS (FA = 0.46) significantly inhibited proliferation of HepG2 cells through vascular absorption on the chip, and inhibited migration of HepG2 cells by inhibiting the formation of pseudopod in liver tumor cells. It was also found that paCOS at 10 μg/mL had a stronger inhibitory effect on liver tumor cells invading blood vessels than that of paCOS at 100 μg/mL, and paCOS at 100 μg/mL, which had a significant destructive effect on tumor vascular growth and barrier function. Moreover, paCOS reduced the number of liver tumor cells adhering onto the surface of HUVECs layer after 3 h of treatment. Therefore, the results revealed that paCOS had considerable potential as drugs for anti-tumor metastasis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of Liver Tumor Cell Metastasis by Partially Acetylated Chitosan Oligosaccharide on A Tumor-Vessel Microsystem

et al. 2019

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“…[ 19 ] Very recently, it was shown that such transwell assays using a microfluidic tumor–vessel co‐culture system are able to demonstrate various phases of cancer metastasis in vitro (e.g., proliferation, migration, intravasation, and adherence). [ 20 ] With the recent development of lab‐on‐a‐chip technology, biochips have been applied to cancer research and, in particular, to cancer cell chemotaxis through confined spaces. [ 6,21 ] Ideally, long, narrow spaces with a hierarchical organization would be used in such studies to offer models with a more in vivo‐like environment.…”

Section: Advantages Of Micro/nanofluidic Glass Biochipsmentioning

confidence: 99%

Mimicking Intravasation–Extravasation with a 3D Glass Nanofluidic Model for the Chemotaxis‐Free Migration of Cancer Cells in Confined Spaces

Sima

Kawano

Hirano

et al. 2020

Adv Materials Technologies

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A new 3D nanofluidic biochip for the study of cancer cell migration and invasion is proposed. In this design, femtosecond laser‐assisted etching is applied to create embedded microfluidic channels, with a base thickness of less than 100 µm for high‐resolution imaging using inverted microscopes. The glass deformation is thermally controlled during fabrication to create pillar‐like formations separated by narrow constricted channels with widths of less than 1 µm spanning lengths of more than tens of microns, mimicking the 3D intravasation–extravasation configuration. Time‐lapse microscopy is used to observe the behavior of prostate cancer (PC3) cells in chemoattractant‐free media over long time intervals as the cells invade the narrow spaces. The PC3 cells are observed to be capable of breaching the fabricated submicrometric intravasation‐like barriers while retaining their viability and proliferation activity. The cells are further able to penetrate the extravasation‐like confining spaces, confirming their dynamic adaptability as they pass through constricted channels with volumes much less than that of the cell nucleus.

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“…Many microsystems were designed to provide a biomimetic environment for in vitro studies [7,[23][24][25][26][27][28]. However, most designed platforms were not fully controlled with desired dimensions.…”

Section: Double-layer Scaffold Platform As Cell Culture Substratementioning

confidence: 99%

Using Biomimetic Scaffold Platform to Detect Growth Factor Induced Changes in Migration Dynamics of Nasopharyngeal Epithelial Cells

Lam

Pang

2020

IEEE Access

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A polydimethylsiloxane two-layer scaffold platform was designed to provide a threedimensional biomimetic microsystem that allows the detection of epithelial-to-mesenchymal transition without the use of specific biomarkers. As a proof of concept, a novel microsystem that consisted of two layers of 15 μm thick grating structures was developed. These layers had gratings with 40 μm wide ridges and 10 μm wide trenches, and they were stacked together to form a scaffold platform. To investigate the feasibility of using the engineered platforms for detecting changes in epithelial-to-mesenchymal transition, transforming growth factor beta-1 was added to an untransformed nasopharyngeal epithelial cell line. On flat polydimethylsiloxane surfaces, transforming growth factor beta-1 did not significantly affect nasopharyngeal epithelial size, migration speed, or directionality. However, the effect of transforming growth factor beta-1 treatment on migration speed of nasopharyngeal epithelial cells cultured on the twolayer scaffold platform was significantly different. Furthermore, while almost no untreated nasopharyngeal epithelial cells could squeeze into the 10 μm wide trenches, 21% of the transforming growth factor beta-1 treated nasopharyngeal epithelial cells exhibited traversing behaviors on the two-layer scaffold platforms. Moreover, fibronectin coating on the trenches and bottom layers of the scaffold platforms further enhanced the transforming growth factor beta-1-induced traversing of nasopharyngeal epithelial cells into the narrow trenches. These results demonstrate that the engineered two-layer scaffold microsystem can be used to monitor epithelial-to-mesenchymal transition induced changes in cell migration and invasiveness, paving the way of using these platforms in high throughput drug screening INDEX TERMS 3D scaffold platform, cell migration, epithelial-to-mesenchymal transition, nasopharyngeal cell, traversing into narrow trenches This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.

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Establishment and application of a dynamic tumor-vessel microsystem for studying different stages of tumor metastasis and evaluating anti-tumor drugs

Abstract: The different stages of the cancer metastasis were reproduced individually on a novel tumor-vessel co-culture microsystem.

Cited by 18 publications

References 47 publications

Inhibition of Liver Tumor Cell Metastasis by Partially Acetylated Chitosan Oligosaccharide on A Tumor-Vessel Microsystem

Inhibition of Liver Tumor Cell Metastasis by Partially Acetylated Chitosan Oligosaccharide on A Tumor-Vessel Microsystem

Mimicking Intravasation–Extravasation with a 3D Glass Nanofluidic Model for the Chemotaxis‐Free Migration of Cancer Cells in Confined Spaces

Using Biomimetic Scaffold Platform to Detect Growth Factor Induced Changes in Migration Dynamics of Nasopharyngeal Epithelial Cells

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