Enhanced cancer cell invasion caused by fibroblasts when fluid flow is present

Urdal, Jone; Waldeland, Jahn Otto; Evje, Steinar

doi:10.1007/s10237-019-01128-2

Cited by 11 publications

(5 citation statements)

References 32 publications

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“…Cell adhesion is one of the important factors in metastasis. The adhesion between tumor cells and their neighbor cells especially fibroblast was investigated in the last two decades 63 , 64 . It has been shown that fibroblasts can act as leader cells in metastasis by providing heterotypic mechanical adhesion to tumor cells 63 , 65 .…”

Section: Discussionmentioning

confidence: 99%

“…The adhesion between tumor cells and their neighbor cells especially fibroblast was investigated in the last two decades 63 , 64 . It has been shown that fibroblasts can act as leader cells in metastasis by providing heterotypic mechanical adhesion to tumor cells 63 , 65 . It is also known that cell adhesion molecules that can act as tumor suppressors are altered in cancer thus the cancer cells may lose these surface molecules 66 .…”

Section: Discussionmentioning

confidence: 99%

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Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model

Moghimi,

Hosseini,

Dalan

et al. 2023

Sci Rep

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Cancer treatment resistance is a caused by presence of various types of cells and heterogeneity within the tumor. Tumor cell–cell and cell-microenvironment interactions play a significant role in the tumor progression and invasion, which have important implications for diagnosis, and resistance to chemotherapy. In this study, we develop 3D bioprinted in vitro models of the breast cancer tumor microenvironment made of co-cultured cells distributed in a hydrogel matrix with controlled architecture to model tumor heterogeneity. We hypothesize that the tumor could be represented by a cancer cell-laden co-culture hydrogel construct, whereas its microenvironment can be modeled in a microfluidic chip capable of producing a chemical gradient. Breast cancer cells (MCF7 and MDA-MB-231) and non-tumorigenic mammary epithelial cells (MCF10A) were embedded in the alginate-gelatine hydrogels and printed using a multi-cartridge extrusion bioprinter. Our approach allows for precise control over position and arrangements of cells in a co-culture system, enabling the design of various tumor architectures. We created samples with two different types of cells at specific initial locations, where the density of each cell type was carefully controlled. The cells were either randomly mixed or positioned in sequential layers to create cellular heterogeneity. To study cell migration toward chemoattractant, we developed a chemical microenvironment in a chamber with a gradual chemical gradient. As a proof of concept, we studied different migration patterns of MDA-MB-231 cells toward the epithelial growth factor gradient in presence of MCF10A cells in different ratios using this device. Our approach involves the integration of 3D bioprinting and microfluidic devices to create diverse tumor architectures that are representative of those found in various patients. This provides an excellent tool for studying the behavior of cancer cells with high spatial and temporal resolution.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model

Moghimi,

Hosseini,

Dalan

et al. 2023

Sci Rep

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“…The cell-fluid two-phase model we are interested in takes the following form (we refer to Refs. 3,4,6,15,28,34,35, and 36 for details):…”

Section: Metastatic Behavior Vs Emtmentioning

confidence: 99%

How Tumor Cells Can Make Use of Interstitial Fluid Flow in a Strategy for Metastasis

Evje

Waldeland

2019

Cel. Mol. Bioeng.

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Introduction-The phenomenon of lymph node metastasis has been known for a long time. However, the underlying mechanism by which malignant tumor cells are able to break loose from the primary tumor site remains unclear. In particular, two competing fluid sensitive migration mechanisms have been reported in the experimental literature: (i) autologous chemotaxis (Shields et al. in Cancer Cell 11:526-538, 2007) which gives rise to downstream migration; (ii) an integrin-mediated and strain-induced upstream mechanism (Polacheck et al. in PNAS 108:11115-11120, 2011). How can these two competing mechanisms be used as a means for metastatic behavior in a realistic tumor setting? Excessive fluid flow is typically produced from leaky intratumoral blood vessels and collected by lymphatics in the peritumoral region giving rise to a heterogeneous fluid velocity field and a corresponding heterogeneous cell migration behavior, quite different from the experimental setup. Method-In order to shed light on this issue there is a need for tools which allow one to extrapolate the observed single cell behavior in a homogeneous microfluidic environment to a more realistic, higher-dimensional tumor setting. Here we explore this issue by using a computational multiphase model. The model has been trained with data from the experimental results mentioned above which essentially reflect one-dimensional behavior. We extend the model to an envisioned idealized two-dimensional tumor setting. Result-A main observation from the simulation is that the autologous chemotaxis migration mechanism, which triggers tumor cells to go with the flow in the direction of lymphatics, becomes much more aggressive and effective as a means for metastasis in the presence of realistic IF flow. This is because the outwardly directed IF flow generates upstream cell migration that possibly empowers small clusters of tumor cells to break loose from the primary tumor periphery. Without this upstream stress-mediated migration, autologous chemotaxis is inclined to move cells at the rim of the tumor in a homogeneous and collective, but space-demanding style. In contrast, inclusion of realistic IF flow generates upstream migration that allows two different aspects to be synthesized: maintain the coherency and solidity of the the primary tumor and at the same time cleave the outgoing waves of tumor cells into small clusters at the front that can move collectively in a more specific direction.

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“…The importance of multiphase flow in porous media has long been recognized in many fields. Mathematical modelling of multiphase flow is essential in practical applications like enhanced oil recovery and geological CO 2 storage in depleted oil and gas reservoirs [25,42] as well as biological processes [29,14,18,39,40,37]. Traditional formulations of multiphase flow describe macroscopic fluid fluxes with a straightforward extension, first proposed by Muskat [30,3], of Darcy's equation for single-phase flow.…”

Section: (Communicated By Paola Goatin)mentioning

confidence: 99%

Compressible and viscous two-phase flow in porous media based on mixture theory formulation

Qiao¹,

Wen²,

Evje³

2019

Networks &Amp; Heterogeneous Media

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The purpose of this work is to carry out investigations of a generalized two-phase model for porous media flow. The momentum balance equations account for fluid-rock resistance forces as well as fluid-fluid drag force effects, in addition, to internal viscosity through a Brinkmann type viscous term. We carry out detailed investigations of a one-dimensional version of the general model. Various a priori estimates are derived that give rise to an existence result. More precisely, we rely on the energy method and use compressibility in combination with the structure of the viscous term to obtain H 1 -estimates as well upper and lower uniform bounds of mass variables. These a priori estimates imply existence of solutions in a suitable functional space for a global time T > 0. We also derive discrete schemes both for the incompressible and compressible case to explore the role of the viscosity term (Brinkmann type) as well as the incompressible versus the compressible case. We demonstrate similarities and differences between a formulation that is based, respectively, on interstitial velocity and Darcy velocity in the viscous term. The investigations may suggest that interstitial velocity seems more natural to use in the formulation of momentum balance than Darcy velocity.

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Enhanced cancer cell invasion caused by fibroblasts when fluid flow is present

Cited by 11 publications

References 32 publications

Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model

Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model

How Tumor Cells Can Make Use of Interstitial Fluid Flow in a Strategy for Metastasis

Compressible and viscous two-phase flow in porous media based on mixture theory formulation

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