Extracellular Matrix Stiffness and Architecture Govern Intracellular Rheology in Cancer

Baker, Erin L.; Bonnecaze, Roger T.; Zaman, Muhammad H.

doi:10.1016/j.bpj.2009.05.054

Cited by 175 publications

(153 citation statements)

References 45 publications

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“…Normal breast tissue is soft (approximately 0.2 kPa), whereas breast tumors are much stiffer (on the order of 4 kPa) (Baker et al, 2009;Levental et al, 2007). Dense and probably stiff breast tissue increases the risk of a patient developing breast cancer.…”

Section: Cancermentioning

confidence: 99%

Mechanisms of mechanical signaling in development and disease

Janmey

Miller

2011

Journal of Cell Science

408

332

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SummaryThe responses of cells to chemical signals are relatively well characterized and understood. Cells also respond to mechanical signals in the form of externally applied force and forces generated by cell-matrix and cell-cell contacts. Many features of cell function that are generally considered to be under the control of chemical stimuli, such as motility, proliferation, differentiation and survival, can also be altered by changes in the stiffness of the substrate to which the cells are adhered, even when their chemical environment remains unchanged. Many examples from clinical and whole animal studies have shown that changes in tissue stiffness are related to specific disease characteristics and that efforts to restore normal tissue mechanics have the potential to reverse or prevent cell dysfunction and disease. How cells detect stiffness is largely unknown, but the cellular structures that measure stiffness and the general principles by which they work are beginning to be revealed. This Commentary highlights selected recent reports of mechanical signaling during disease development, discusses open questions regarding the physical mechanisms by which cells sense stiffness, and examines the relationship between studies in vitro on flat substrates and the more complex three-dimensional setting in vivo.

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Section: Cancermentioning

confidence: 99%

Mechanisms of mechanical signaling in development and disease

Janmey

Miller

2011

Journal of Cell Science

408

332

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“…Finally, the physical barriers to invasion also relate to physical factors, such as the relative stiffness of the tissue and other features. Models to study these physical factors are underway in many laboratories (42). Evidence from several groups has implicated b1 integrin regulators such as transforming growth factor b and urokinase plasminogen activator receptor (43)(44)(45), as well as downstream pathways such as Src kinase (SRC), focal adhesion kinase (FAK), and pre activated kinase (PAK) in thyroid cancer progression (46,47).…”

Section: Extracellular Matrixmentioning

confidence: 99%

Metastatic Dormancy and Progression in Thyroid Cancer: Targeting Cells in the Metastatic Frontier

Ringel

2011

Thyroid

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Background: Metastatic dormancy, or the ability of cancer cells to survive but not progress in metastatic environments, is now recognized to be a common occurrence in cancer. Summary: From a clinical perspective, this phenomenon is common in metastatic well-differentiated thyroid cancer, whereby patients often present with distant metastases that remain stable for years after removal of the primary tumor and subsequent treatment. Experimental data suggest that metastases can develop throughout the life of a cancer and that progression in the distant environment depends on the biology of the cancer cells that metastasize as well as that of the various microenvironments they encounter. A firm understanding of how thyroid cancer cell progression is regulated in different metastatic environments is necessary to devise effective therapies targeting progressive metastatic thyroid cancer. Conclusion: In this review, current models of metastatic progression and factors that regulate late-stage metastatic progression that are particularly relevant for thyroid cancer are discussed.

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“…Additionally, higher speed could be due to low adhesion structures in response to reduced matrix stiffness in comparison to the coating. As such, when integrin binding is blocked, the biochemical information conveyed by the receptor is absent and matrix stiffness governs cell migratory behavior [43]. It is also possible that fibrosarcoma cells switch their migration mode from mesenchymal to amoeboid when interacting with 3D fibrillar FN matrices.…”

Section: α 5 β 1 -Integrin Binding To Fibronectin Modulates Tumor Celmentioning

confidence: 99%

$$\upalpha 5\upbeta $$ α 5 β 1-integrin and MT1-MMP promote tumor cell migration in 2D but not in 3D fibronectin microenvironments

et al. 2014

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Cell migration is a crucial event for physiological processes, such as embryonic development and wound healing, as well as for pathological processes, such as cancer dissemination and metastasis formation. Cancer cell migration is a result of the concerted action of matrix metalloproteinases (MMPs), expressed by cancer cells to degrade the surrounding matrix, and integrins, the transmembrane receptors responsible for cell binding to matrix proteins. While it is known that cell-microenvironment interactions are essential for migration, the role of the physical state of such interactions remains still unclear. In this study we investigated human fibrosarcoma cell migration in two-dimensional (2D) and three-dimensional (3D) fibronectin (FN) microenvironments. By using antibody blocking approach and cellbinding site mutation, we determined that α 5 β 1 -integrin is Electronic supplementary material The online version of this article (doi:10.1007/s00466-013-0960-6) contains supplementary material, which is available to authorized users. the main mediator of fibrosarcoma cell migration in 2D FN, whereas in 3D fibrillar FN, the binding of α 5 β 1 -and α v β 3 -integrins is not necessary for cell movement in the fibrillar network. Furthermore, while the general inhibition of MMPs with GM6001 has no effect on cell migration in both 2D and 3D FN matrices, we observed opposing effect after targeted silencing of a membrane-bound MMP, namely MT1-MMP. In 2D fibronectin, silencing of MT1-MMP results in decreased migration speed and loss of directionality, whereas in 3D FN matrices, cell migration speed is increased and integrin-mediated signaling for actin dynamics is promoted. Our results suggest that the fibrillar nature of the matrix governs the migratory behavior of fibrosarcoma cells. Therefore, to hinder migration and dissemination of diseased cells, matrix molecules should be directly targeted, rather than specific subtypes of receptors at the cell membrane.

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Extracellular Matrix Stiffness and Architecture Govern Intracellular Rheology in Cancer

Cited by 175 publications

References 45 publications

Mechanisms of mechanical signaling in development and disease

Mechanisms of mechanical signaling in development and disease

Metastatic Dormancy and Progression in Thyroid Cancer: Targeting Cells in the Metastatic Frontier

$$\upalpha 5\upbeta $$ α 5 β 1-integrin and MT1-MMP promote tumor cell migration in 2D but not in 3D fibronectin microenvironments

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