Effects of biomechanical forces on the biological behavior of cancer stem cells

Tian, Bo; Wei, Lin; Zhang, Yan

doi:10.7150/jca.60893

Cited by 13 publications

(21 citation statements)

References 83 publications

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“…The occurrence of cells or nodules outside the gels could reflect invasion or metastasis. One important contributor to invasion and metastasis, is EMT, which is driven—at least in part—by ECM components, soluble factors, and hypoxia 20 , 21 , 29 . To determine whether this was a contributing factor behind the population of cells found outside of the gels, we investigated known markers of EMT.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in ECM composition are one of the characterizing features of the TME and it is widely accepted that this actively contributes to disease progression in different tumors 20,21 . This significance of altered ECM is seen in HCC patients, where increases in liver stiffness are associated with hepatic dysfunction, poor prognosis, and survival [22][23][24] .…”

Section: Discussionmentioning

confidence: 99%

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Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma

Calitz

Rosenquist

Degerstedt

et al. 2023

Sci Rep

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The tumor micro-environment (TME) of hepatocellular carcinoma (HCC) consists out of cirrhotic liver tissue and is characterized by an extensive deposition of extracellular matrix proteins (ECM). The evolution from a reversible fibrotic state to end-stage of liver disease, namely cirrhosis, is characterized by an increased deposition of ECM, as well as changes in the exact ECM composition, which both contribute to an increased liver stiffness and can alter tumor phenotype. The goal of this study was to assess how changes in matrix composition and stiffness influence tumor behavior. HCC-cell lines were grown in a biomimetic hydrogel model resembling the stiffness and composition of a fibrotic or cirrhotic liver. When HCC-cells were grown in a matrix resembling a cirrhotic liver, they increased proliferation and protein content, compared to those grown in a fibrotic environment. Tumour nodules spontaneously formed outside the gels, which appeared earlier in cirrhotic conditions and were significantly larger compared to those found outside fibrotic gels. These tumor nodules had an increased expression of markers related to epithelial-to-mesenchymal transition (EMT), when comparing cirrhotic to fibrotic gels. HCC-cells grown in cirrhotic gels were also more resistant to doxorubicin compared with those grown in fibrotic gels or in 2D. Therefore, altering ECM composition affects tumor behavior, for instance by increasing pro-metastatic potential, inducing EMT and reducing response to chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma

Calitz

Rosenquist

Degerstedt

et al. 2023

Sci Rep

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“…This mechanical stress made by cells and structures in the cellular environment seems to drive multiple behaviors, such as cellular morphogenesis, the epithelial-to-mesenchymal transition (EMT), and consequent cancer development and dissemination. Stiffness, in turn, is prompted by the accumulation of the extracellular matrix (ECM), since pressure can modulate cellular response to the activity of proliferation, differentiation, and migration [ 98 , 99 ]. In particular, signals controlling stiffness are regulated by the intracellular PI3K/Akt-mTOR-SOX2 pathway through the transmembrane protein integrin-β1 (ITGB1), with a high expression of CD133 and epithelial cell adhesion molecules (EpCAM) [ 100 ].…”

Section: Cscs In Tumor Growth and Dissemination: The Quiescent And Th...mentioning

confidence: 99%

“…In addition, there are other stimuli, such as integrins, the presence of the epithelial receptor CD44, increased expression of SOX2, OCT4, and NANOG. ; which induce non-CSCs to transform into CSCs through ECM modifications [ 98 , 99 , 100 , 101 , 102 ], and this inclines towards a poor prognosis. ( Figure 2 ).…”

Section: Cscs In Tumor Growth and Dissemination: The Quiescent And Th...mentioning

confidence: 99%

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Aramini

Masciale

Grisendi

et al. 2022

Cancers

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Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs’ self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process.

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“…In addition to its important role in maintaining homeostasis, its movement creates shear stress on the cell surface. The shear stress is known to affect tumor proliferation and apoptosis 18 , epithelial–mesenchymal transition 19 , behavior of cancer stem cells 20 , and metastasis 21 . Thus, this mechanistical force is an essential factor in the functioning of healthy and neoplastic cells.…”

Section: Introductionmentioning

confidence: 99%

Establishing a simple perfusion cell culture system for light-activated liposomes

Mäki-Mikola

Laurén

Uema

et al. 2023

Sci Rep

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The off-target effects of light-activated or targeted liposomes are difficult to distinguish in traditional well plate experiments. Additionally, the absence of fluid flow in traditional cell models can lead to overestimation of nanoparticle uptake. In this paper, we established a perfusion cell culture platform to study light-activated liposomes and determined the effect of flow on the liposomal cell uptake. The optimal cell culturing parameters for the A549 cells under flow conditions were determined by monitoring cell viability. To determine optimal liposome treatment times, particle uptake was measured with flow cytometry. The suitability of commercial QuasiVivo flow-chambers for near-infrared light activation was assessed with a calcein release study. The chamber material did not hinder the light activation and subsequent calcein release from the liposomes. Furthermore, our results show that the standard cell culturing techniques are not directly translatable to flow cultures. For non-coated liposomes, the uptake was hindered by flow. Interestingly, hyaluronic acid coating diminished the uptake differences between the flow and static conditions. The study demonstrates that flow affects the liposomal uptake by lung cancer cell line A549. The flow also complicates the cell attachment of A549 cells. Moreover, we show that the QuasiVivo platform is suitable for light-activation studies.

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Effects of biomechanical forces on the biological behavior of cancer stem cells

Cited by 13 publications

References 83 publications

Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma

Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Establishing a simple perfusion cell culture system for light-activated liposomes

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