Circulating prostate cancer cells have differential resistance to fluid shear stress-induced cell death

Hope, Jacob M.; Bersi, Matthew R.; Dombroski, Jenna A.; Pereles, Rebecca S.; Merryman, W. David; King, Michael R.

doi:10.1242/jcs.251470

Cited by 26 publications

(32 citation statements)

References 56 publications

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“…1A). However, FSS at sufficient magnitude has previously been shown to be cytotoxic to cells [20]. Levels of shear stress as high as 1000 dyn/cm 2 are experienced at bifurcations in the heart and can damage the structure of cells [21].…”

Section: Fss Enhances Zap70 Phosphorylation In Jurkat Cells Treated W...mentioning

confidence: 99%

Fluid shear stress enhances T cell activation through Piezo1

et al. 2022

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Background T cell activation is a mechanical process as much as it is a biochemical process. In this study, we used a cone-and-plate viscometer system to treat Jurkat and primary human T cells with fluid shear stress (FSS) to enhance the activation of the T cells through mechanical means. Results The FSS treatment of T cells in combination with soluble and bead-bound CD3/CD28 antibodies increased the activation of signaling proteins essential for T cell activation, such as zeta-chain-associated protein kinase-70 (ZAP70), nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), and AP-1 (activator protein 1). The FSS treatment also enhanced the expression of the cytokines tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2), and interferon gamma (IFN-γ), which are necessary for sustained T cell activation and function. The enhanced activation of T cells by FSS was calcium dependent. The calcium signaling was controlled by the mechanosensitive ion channel Piezo1, as GsMTx-4 and Piezo1 knockout reduced ZAP70 phosphorylation by FSS. Conclusions These results demonstrate an intriguing new dynamic to T cell activation, as the circulatory system consists of different magnitudes of FSS and could have a proinflammatory role in T cell function. The results also identify a potential pathophysiological relationship between T cell activation and FSS, as hypertension is a disease characterized by abnormal blood flow and is correlated with multiple autoimmune diseases.

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Section: Fss Enhances Zap70 Phosphorylation In Jurkat Cells Treated W...mentioning

confidence: 99%

Fluid shear stress enhances T cell activation through Piezo1

et al. 2022

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“…In circulation, cancer cells are exposed to elevated fluid shear stresses that can cause damage to the cells and lead to cell death [ 5 , 6 ]. Thus, cells must develop mechanisms of resisting the damage by these physical forces [ 7 ]. When exiting the circulatory system, cancer cells must tether to the endothelium, pass through the endothelial wall, and begin invading the distant site [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Channeling the Force: Piezo1 Mechanotransduction in Cancer Metastasis

Dombroski

Hope

Sarna

et al. 2021

Cells

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Cancer metastasis is one of the leading causes of death worldwide, motivating research into identifying new methods of preventing cancer metastasis. Recently there has been increasing interest in understanding how cancer cells transduce mechanical forces into biochemical signals, as metastasis is a process that consists of a wide range of physical forces. For instance, the circulatory system through which disseminating cancer cells must transit is an environment characterized by variable fluid shear stress due to blood flow. Cancer cells and other cells can transduce physical stimuli into biochemical responses using the mechanosensitive ion channel Piezo1, which is activated by membrane deformations that occur when cells are exposed to physical forces. When active, Piezo1 opens, allowing for calcium flux into the cell. Calcium, as a ubiquitous second-messenger cation, is associated with many signaling pathways involved in cancer metastasis, such as angiogenesis, cell migration, intravasation, and proliferation. In this review, we discuss the roles of Piezo1 in each stage of cancer metastasis in addition to its roles in immune cell activation and cancer cell death.

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“…Shear stress occurs when neighboring layers of fluid (blood) and viscosity move at different speeds, influencing the translational and rotational motion of CTCs and perhaps causing the deformation of CTCs, making them vulnerable to physical damages of fluidic force and immune cell attack. In arterial circulation, the fluid shear stress encountered by cancer cells is 0.4–3 Pa and 0.05–0.4 Pa in venous circulation [ 84 ]. Extravasation is aided by the adhesion of cancer cells to endothelial cells caused by fluid shear stress [ 85 ].…”

Section: Microfluidic Devices In Cancer Researchmentioning

confidence: 99%

Applications of Microfluidics and Organ-on-a-Chip in Cancer Research

et al. 2022

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Taking the life of nearly 10 million people annually, cancer has become one of the major causes of mortality worldwide and a hot topic for researchers to find innovative approaches to demystify the disease and drug development. Having its root lying in microelectronics, microfluidics seems to hold great potential to explore our limited knowledge in the field of oncology. It offers numerous advantages such as a low sample volume, minimal cost, parallelization, and portability and has been advanced in the field of molecular biology and chemical synthesis. The platform has been proved to be valuable in cancer research, especially for diagnostics and prognosis purposes and has been successfully employed in recent years. Organ-on-a-chip, a biomimetic microfluidic platform, simulating the complexity of a human organ, has emerged as a breakthrough in cancer research as it provides a dynamic platform to simulate tumor growth and progression in a chip. This paper aims at giving an overview of microfluidics and organ-on-a-chip technology incorporating their historical development, physics of fluid flow and application in oncology. The current applications of microfluidics and organ-on-a-chip in the field of cancer research have been copiously discussed integrating the major application areas such as the isolation of CTCs, studying the cancer cell phenotype as well as metastasis, replicating TME in organ-on-a-chip and drug development. This technology’s significance and limitations are also addressed, giving readers a comprehensive picture of the ability of the microfluidic platform to advance the field of oncology.

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Circulating prostate cancer cells have differential resistance to fluid shear stress-induced cell death

Cited by 26 publications

References 56 publications

Fluid shear stress enhances T cell activation through Piezo1

Fluid shear stress enhances T cell activation through Piezo1

Channeling the Force: Piezo1 Mechanotransduction in Cancer Metastasis

Applications of Microfluidics and Organ-on-a-Chip in Cancer Research

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