Cell-matrix adhesion characterization using multiple shear stress zones in single stepwise microchannel

Kim, Min Ji; Doh, Il; Bae, Gab-Yong; Cha, Hyuk‐Jin; Cho, Young-Ho

doi:10.1063/1.4892666

Cited by 5 publications

(3 citation statements)

References 26 publications

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“…The question remains as to how Akt activity was elevated in TD cells after TGFβ stimulation. Previously, we have reported that lung cancer cells become resistant to sheer stress after EMT [ 25 ], which is consistent with previously reported findings [ 26 ]. Based on this observation, we attempted to deduce a gene candidate(s) whose altered expression in TD cells contributes to both increased adhesion (e.g., resistance to sheer stress) and intracellular signaling (e.g., toward GSK3β).…”

Section: Resultssupporting

confidence: 93%

Chronic TGFβ stimulation promotes the metastatic potential of lung cancer cells by Snail protein stabilization through integrin β3-Akt-GSK3β signaling

et al. 2016

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Chronic exposure to TGFβ, a frequent occurrence for tumor cells in the tumor microenvironment, confers more aggressive phenotypes on cancer cells by promoting their invasion and migration while at the same time increasing their resistance to the growth-inhibitory effect of TGFβ. In this study, a transdifferentiated (TD) A549 cell model, established by chronically exposing A549 cells to TGFβ, showed highly invasive phenotypes in conjunction with attenuation of Smad-dependent signaling. We show that Snail protein, the mRNA expression of which strongly correlates with a poor prognosis in lung cancer patients, was highly stable in TD cells after TGFβ stimulation. The increased protein stability of Snail in TD cells correlated with elevated inhibitory phosphorylation of GSK3β, resulting from the high Akt activity. Notably, integrin β3, whose expression was markedly increased upon sustained exposure to TGFβ, was responsible for the high Akt activity as well as the increased Snail protein stability in TD cells. Consistently, clinical database analysis on lung cancer patients revealed a negative correlation between overall survival and integrin β3 mRNA levels. Therefore, we suggest that the integrin β3-Akt-GSK3β signaling axis plays an important role in non-canonical TGFβ signaling, determining the invasive properties of tumor cells chronically exposed to TGFβ.

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Section: Resultssupporting

confidence: 93%

Chronic TGFβ stimulation promotes the metastatic potential of lung cancer cells by Snail protein stabilization through integrin β3-Akt-GSK3β signaling

et al. 2016

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“…In our previous work [48], we demonstrated long-term cell culture and cytotoxicity assay using different PDMS devices. Previously, we also performed 6 h cultivation for sufficient cell adhesion to PDMA surfaces [49]. In this study we verified and lowered the incubation time to 3 h, by which time most of the seeded cells had adhered well on the device.…”

Section: Cell Impedance Analysissupporting

confidence: 55%

A cell impedance measurement device for the cytotoxicity assay dependent on the velocity of supplied toxic fluid

Kang

Kim

Cho

2018

J. Micromech. Microeng.

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We present a cell impedance measurement chip capable of characterizing the toxic response of cells depending on the velocity of the supplied toxic fluid. Previous impedance-based devices using a single open-top chamber have been limited to maintaining a constant supply velocity, and devices with a single closed-top chamber present difficulties in simultaneous cytotoxicity assay for varying levels of supply velocities. The present device, capable of generating constant and multiple levels of toxic fluid velocity simultaneously within a single stepwise microchannel, performs a cytotoxicity assay dependent on toxic fluid velocity, in order to find the effective velocity of toxic fluid to cells for maximizing the cytotoxic effect. We analyze the cellular toxic response of 5% ethanol media supplied to cancer cells within a toxic fluid velocity range of 0–8.3 mm s−1. We observe the velocity-dependent cell detachment rate, impedance, and death rate. We find that the cell detachment rate decreased suddenly to 2.4% at a velocity of 4.4 mm s−1, and that the change rates of cell resistance and cell capacitance showed steep decreases to 8% and 41%, respectively, at a velocity of 5.7 mm s−1. The cell death rate and impedance fell steeply to 32% at a velocity of 5.7 mm s−1. We conclude that: (1) the present device is useful in deciding on the toxic fluid velocity effective to cytotoxicity assay, since the cellular toxic response is dependent on the velocity of toxic fluid, and; (2) the cell impedance analysis facilitates a finer cellular response analysis, showing better correlation with the cell death rate, compared to conventional visual observation. The present device, capable of performing the combinational analysis of toxic fluid velocity and cell impedance, has potential for application to the fine cellular toxicity assay of drugs with proper toxic fluid velocity.

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“…A vital characteristic of cancer metastasis is induction of EMT, which is associated with interaction with the extracellular matrix (20). In the extracellular matrix, the role of the cellular factors is to communicate with the intracellular matrix and a number of these factors have been reported to be associated with EMT, including IL-6, IL-8, VEGF, TGFβ, SNAIL, MMP, TNFα and TWIST.…”

Section: Emt and Tumorigenesismentioning

confidence: 99%

Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis

et al. 2017

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Abstract. Epithelial-mesenchymal transition (EMT) is a biological process that is associated with cancer metastasis and invasion. In cancer, EMT promotes cell motility, invasion and distant metastasis. Interleukin (IL)-8 is highly expressed in tumors and may induce EMT. The IL-8/IL-8R axis has a vital role in EMT in carcinoma, which is regulated by several signaling pathways, including the transforming growth factor β-spleen associated tyrosine kinase/Src-AKT/extracellular signal-regulated kinase, p38/Jun N-terminal kinase-activating transcription factor-2, phosphoinositide 3-kinase/AKT, nuclear factor-κB and Wnt signaling pathways. Blocking the IL-8/IL-8R signaling pathway may be a novel strategy to reduce metastasis and improve patient survival rates. This review will cover IL-8-IL-8R signaling pathway in tumor epithelial-mesenchymal transition.

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Cell-matrix adhesion characterization using multiple shear stress zones in single stepwise microchannel

Cited by 5 publications

References 26 publications

Chronic TGFβ stimulation promotes the metastatic potential of lung cancer cells by Snail protein stabilization through integrin β3-Akt-GSK3β signaling

Chronic TGFβ stimulation promotes the metastatic potential of lung cancer cells by Snail protein stabilization through integrin β3-Akt-GSK3β signaling

A cell impedance measurement device for the cytotoxicity assay dependent on the velocity of supplied toxic fluid

Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis

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