Stress Clamp Experiments on Multicellular Tumor Spheroids

Montel, Fabien; Delarue, Morgan; Elgeti, Jens; Malaquin, Laurent; Basan, Markus; Risler, Thomas; Cabane, Bernard; Vignjević, Danijela; Prost, Jacques; Cappello, Giovanni; Joanny, Jean‐François

doi:10.1103/physrevlett.107.188102

Cited by 200 publications

(253 citation statements)

References 21 publications

(23 reference statements)

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“…These spherical organoids have the same crypt architecture, with minimal physiological environment, suggesting that the organization of the crypt structure can be understood from purely mechanical principles. Spherical organoids allow for controlled experiments on which one could test these theories, following cells in real time, and exerting pressure on them, similarly to [32], in order to test the effect on growth and stem cell dynamics.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, recent experiments on colon carcinoma cells in three dimensions have shown that exerting mechanical pressure on an aggregate lowers its division rate in a significant and predictable way [32]. Therefore, in the following section, we make the additional assumptions that pressurebased growth is sufficient to regulate the first stages of crypt development ðk À k d / ðP À P h ÞÞ and that the regulation of cell division rate is proportional to the fraction of the proliferative compartment which we label…”

Section: Stem Cell Kinetics and Homeostasis Regulationmentioning

confidence: 99%

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Growth, homeostatic regulation and stem cell dynamics in tissues

Hannezo

Prost

Joanny

2014

J. R. Soc. Interface.

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The regulation of cell growth in animal tissues is a question of critical importance: most tissues contain different types of cells in interconversion and the fraction of each type has to be controlled in a precise way, by mechanisms that remain unclear. Here, we provide a theoretical framework for the homeostasis of stem-cell-containing epithelial tissues using mechanical equations, which describe the size of the tissue and kinetic equations, which describe the interconversions of the cell populations. We show that several features, such as the evolution of stem cell fractions during intestinal development, the shape of a developing intestinal wall, as well as the increase in the proliferative compartment in cancer initiation, can be studied and understood from generic modelling which does not rely on a particular regulatory mechanism. Finally, inspired by recent experiments, we propose a model where cell division rates are regulated by the mechanical stresses in the epithelial sheet. We show that pressure-controlled growth can, in addition to the previous features, also explain with few parameters the formation of stem cell compartments as well as the morphologies observed when a colonic crypt becomes cancerous. We also discuss optimal strategies of wound healing, in connection with experiments on the cornea.

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Section: Discussionmentioning

confidence: 99%

Section: Stem Cell Kinetics and Homeostasis Regulationmentioning

confidence: 99%

Growth, homeostatic regulation and stem cell dynamics in tissues

Hannezo

Prost

Joanny

2014

J. R. Soc. Interface.

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“…[2,3,4]. It is interesting to notice that compressive stresses of slightly less than 1 kPa applied through a piston were recently found to induce a metastatic phenotype in cancer cells [7].…”

Section: Introductionmentioning

confidence: 99%

“…Another possibility is that mechanical stresses directly regulate the growth and death rates of cancer cells. Recently, Montel et al have explored this possibility, investigating the effect of a constant stress applied on cellular spheroids over long time scales by inducing osmotic pressure by a solution of dextran, a biocompatible polymer which is neutral and can not be metabolised by mammalian cells [2,3]. Using a similar method, some of us recently reported that a constant low osmotic pressure (1kPa) affects more strongly the proliferative capability of primary human melanoma cells (IgR39) in comparison to the corresponding metastatic ones (IgR37) [4].…”

Section: Introductionmentioning

confidence: 99%

Osmotic stress affects functional properties of human melanoma cell lines

et al. 2015

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Abstract. Understanding the role of microenvironment in cancer growth and metastasis is a key issue for cancer research. Here, we study the effect of osmotic pressure on the functional properties of primary and metastatic melanoma cell lines. In particular, we experimentally quantify individual cell motility and transmigration capability. We then perform a circular scratch assay to study how a cancer cell front invades an empty space. Our results show that primary melanoma cells are sensitive to a low osmotic pressure, while metastatic cells are less. To better understand the experimental results, we introduce and study a continuous model for the dynamics of a cell layer and a stochastic discrete model for cell proliferation and diffusion. The two models capture essential features of the experimental results and allow to make predictions for a wide range of experimentally measurable parameters. PACS. PACS-key discribing text of that key -PACS-key discribing text of that key

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“…Such signalling is mediated through the presence of boundaries, whose shapes determine the formation of morphogen gradients [3] and the local stress state, which in turn controls cell proliferation [4], differentiation [5] and apoptosis [6,7]. Depending on the physical environment, these boundaries may either be static, as is the case for solid substrates, or they may move as new tissue is formed [8].…”

Section: Introductionmentioning

confidence: 99%

Tissue growth controlled by geometric boundary conditions: a simple model recapitulating aspects of callus formation and bone healing

Fischer

Zickler

Dunlop

et al. 2015

J. R. Soc. Interface.

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The shape of tissues arises from a subtle interplay between biochemical driving forces, leading to cell growth, division and extracellular matrix formation, and the physical constraints of the surrounding environment, giving rise to mechanical signals for the cells. Despite the inherent complexity of such systems, much can still be learnt by treating tissues that constantly remodel as simple fluids. In this approach, remodelling relaxes all internal stresses except for the pressure which is counterbalanced by the surface stress. Our model is used to investigate how wettable substrates influence the stability of tissue nodules. It turns out for a growing tissue nodule in free space, the model predicts only two states: either the tissue shrinks and disappears, or it keeps growing indefinitely. However, as soon as the tissue wets a substrate, stable equilibrium configurations become possible. Furthermore, by investigating more complex substrate geometries, such as tissue growing at the end of a hollow cylinder, we see features reminiscent of healing processes in long bones, such as the existence of a critical gap size above which healing does not occur. Despite its simplicity, the model may be useful in describing various aspects related to tissue growth, including biofilm formation and cancer metastases.

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Stress Clamp Experiments on Multicellular Tumor Spheroids

Cited by 200 publications

References 21 publications

Growth, homeostatic regulation and stem cell dynamics in tissues

Growth, homeostatic regulation and stem cell dynamics in tissues

Osmotic stress affects functional properties of human melanoma cell lines

Tissue growth controlled by geometric boundary conditions: a simple model recapitulating aspects of callus formation and bone healing

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