Fluid shear stress in a logarithmic microfluidic device enhances cancer cell stemness marker expression

Dash, Sanat Kumar; Patra, Bamadeb; Sharma, Vineeta; Das, Sarit K.; Verma, Rama Shanker

doi:10.1039/d1lc01139a

Cited by 9 publications

(6 citation statements)

References 51 publications

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“…This work found a correlation between increasing shear stress magnitude [0.01–10 dyne/cm 2 ] and enhancement of stemness-related genes Sox2 and N-cadherin. 42 The up-regulation of N-cadherin, in particular, is also interesting because it indicates a motile mesenchymal genotype. 43 Similarly, in a study on colorectal cancer cells, the application of multiple values of laminar shear stress [0–20 dyne/cm 2 ] via a microfluidic bioreactor resulted in an upregulation of ATOH8, a mechanosensor that contributes to circulating tumor cell survival ( Fig.…”

Section: Bioengineering Strategies To Study Cancer Cell Response To S...mentioning

confidence: 99%

“…Similarly, the variation of mechanical force intensity throughout the body and how it may affect malignancy has recently been explored. 42,117 Mechanical memory, or the continued response to past mechanical environments, of both cancer and cancer-related cells is also an important emerging area of study. 118–120 The idea that cells can commit to memory a past mechanical stimulus and continue to alter their response is fascinating.…”

Section: Conclusion and Future Perspectives: Mechanical Forces In Con...mentioning

confidence: 99%

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Advances in cancer mechanobiology: Metastasis, mechanics, and materials

Clevenger,

McFarlin,

Gorley

et al. 2024

APL Bioengineering

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Within the tumor microenvironment (TME), tumor cells are exposed to numerous mechanical forces, both internally and externally, which contribute to the metastatic cascade. From the initial growth of the tumor to traveling through the vasculature and to the eventual colonization of distant organs, tumor cells are continuously interacting with their surroundings through physical contact and mechanical force application. The mechanical forces found in the TME can be simplified into three main categories: (i) shear stress, (ii) tension and strain, and (iii) solid stress and compression. Each force type can independently impact tumor growth and progression. Here, we review recent bioengineering strategies, which have been employed to establish the connection between mechanical forces and tumor progression. While many cancers are explored in this review, we place great emphasis on cancers that are understudied in their response to mechanical forces, such as ovarian and colorectal cancers. We discuss the major steps of metastatic transformation and present novel, recent advances in model systems used to study how mechanical forces impact the study of the metastatic cascade. We end by summarizing systems that incorporate multiple forces to expand the complexity of our understanding of how tumor cells sense and respond to mechanical forces in their environment. Future studies would also benefit from the inclusion of time or the aspect of mechanical memory to further enhance this field. While the knowledge of mechanical forces and tumor metastasis grows, developing novel materials and in vitro systems are essential to providing new insight into predicting, treating, and preventing cancer progression and metastasis.

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Section: Bioengineering Strategies To Study Cancer Cell Response To S...mentioning

confidence: 99%

Section: Conclusion and Future Perspectives: Mechanical Forces In Con...mentioning

confidence: 99%

Advances in cancer mechanobiology: Metastasis, mechanics, and materials

Clevenger,

McFarlin,

Gorley

et al. 2024

APL Bioengineering

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show abstract

“…Living cells will experience several different levels of FSS when they stay in blood circulation 22 . FSS fluctuates between 0.4 and 6 Pa in veins, arteries, lymphatics and capillaries 24,25 . Although the detailed mechanism is not very clear yet, it was found that FSS in the blood could increase the level of reactive oxygen species (ROS) in cells, thus damaging their mitochondria and inducing cell death 26,27 .…”

Section: Introductionmentioning

confidence: 99%

Reducing cholesterol level in membrane of live macrophages improves their delivery performance by enhancing adaptation to blood shear stress

Zhang,

Li,

et al. 2023

Preprint

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In recent years, the live cells-based drug delivery systems have attracted much interests. However, shear stress in the blood flow may cause cell death and waken their delivery performances. In this study, we found that reducing cholesterol in macrophages enhanced its tumor targeting ability by more than 2-fold. Mechanism study indicates that the reduced cholesterol in macrophages deactivated the mammalian target of rapamycin (mTOR) and consequent promoted transcription factor EB (TFEB) nucleus translocation, which enhances the expression of superoxide dismutase (SOD) in cells to reduce reactive oxygen species (ROS) induced by the flow shear stress. A proof-of-concept system using low cholesterol macrophages attached MXene (l-RX) is thus fabricated. On melanoma mice model, tumors are eliminated with no recurrence in all mice after treated with l-RX and laser irradiation. Therefore, we develop a simple and effective way to enhance the targeting performance of macrophage-based drug delivery systems.

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“…27−29 Generally, FSS levels fluctuate between 0.4 and 6 Pa in veins, arteries, lymphatics and capillaries; this is strong enough to effectively stimulate mechanical force-sensing pathways in cells. 30,31 It has been reported that blood FSS may increase the level of reactive oxygen species (ROS) in cells, which damages their mitochondria and induces cell death. 32,33 Thus, enhancing the adaptability of cells to FSS may improve their survival rate in the blood.…”

mentioning

confidence: 99%

“…However, compared with common delivery vehicles, such as polymeric nanoparticles and extracellular vesicles, living cells are generally more sensitive to the in vivo environment. − This is because, in many cases, they are larger, more complex, more fragile, and naturally responsive to various biological signals, which may diminish their targeting function . As intravenous injection is the major route of drug administration whereby delivery vehicles are directly injected into the blood, − one important aspect of the in vivo environment is fluid shear stress (FSS), which occurs due to the blood flow. − Generally, FSS levels fluctuate between 0.4 and 6 Pa in veins, arteries, lymphatics and capillaries; this is strong enough to effectively stimulate mechanical force-sensing pathways in cells. , It has been reported that blood FSS may increase the level of reactive oxygen species (ROS) in cells, which damages their mitochondria and induces cell death. , Thus, enhancing the adaptability of cells to FSS may improve their survival rate in the blood …”

mentioning

confidence: 99%

Reducing Cholesterol Level in Live Macrophages Improves Delivery Performance by Enhancing Blood Shear Stress Adaptation

Zhang,

Li,

et al. 2023

Nano Lett.

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In recent years, live-cell-based drug delivery systems have gained considerable attention. However, shear stress, which accompanies blood flow, may cause cell death and weaken the delivery performance. In this study, we found that reducing cholesterol in macrophage plasma membranes enhanced their tumor targeting ability by more than 2-fold. Our study demonstrates that the reduced cholesterol level deactivated the mammalian target of rapamycin (mTOR) and consequently promoted the nuclear translocation of transcription factor EB (TFEB), which in turn enhanced the expression of superoxide dismutase (SOD) to reduce reactive oxygen species (ROS) induced by shear stress. A proof-of-concept system using low cholesterol macrophages attached to MXene (e.g., l-RX) was fabricated. In a melanoma mouse model, l-RX and laser irradiation treatments eliminated tumors with no recurrences observed in mice. Therefore, cholesterol reduction is a simple and effective way to enhance the targeting performance of macrophage-based drug delivery systems.

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Fluid shear stress in a logarithmic microfluidic device enhances cancer cell stemness marker expression

Abstract: Our logarithmic microfluidic device shows the dependence of cancer metastasis, recurrence and drug resistance on fluid shear stress mechanotransduction in cancer microenvironment and circulation.

Cited by 9 publications

References 51 publications

Advances in cancer mechanobiology: Metastasis, mechanics, and materials

Advances in cancer mechanobiology: Metastasis, mechanics, and materials

Reducing cholesterol level in membrane of live macrophages improves their delivery performance by enhancing adaptation to blood shear stress

Reducing Cholesterol Level in Live Macrophages Improves Delivery Performance by Enhancing Blood Shear Stress Adaptation

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